Memantine before Mastectomy Prevents Post-Surgery Pain: A Randomized,Blinded Clinical Trial in Surgical Patients

BackgroundNeuropathic pain following surgical treatment for breast cancer with or without chemotherapy is a clinical burden and patients frequently report cognitive, emotional and quality of life impairment. A preclinical study recently showed that memantine administered before surgery may prevent neuropathic pain development and cognitive dysfunction. With a translational approach, a clinical trial has been carried out to evaluate whether memantine administered before and after mastectomy could prevent the development of neuropathic pain, the impairment of cognition and quality of life.MethodA randomized, pilot clinical trial included 40 women undergoing mastectomy in the Oncology Department, University Hospital, Clermont-Ferrand, France. Memantine (5 to 20 mg/day; n = 20) or placebo (n = 20) was administered for four weeks starting two weeks before surgery. The primary endpoint was pain intensity measured on a (0–10) numerical rating scale at three months post-mastectomy.ResultsData analyses were performed using mixed models and the tests were two-sided, with a type I error set at α = 0.05. Compared with placebo, patients receiving memantine showed at three months a significant difference in post-mastectomy pain intensity, less rescue analgesia and a better emotional state. An improvement of pain symptoms induced by cancer chemotherapy was also reported.ConclusionsThis study shows for the first time the beneficial effect of memantine to prevent post-mastectomy pain development and to diminish chemotherapy-induced pain symptoms. The lesser analgesic consumption and better well-being of patients for at least six months after treatment suggests that memantine could be an interesting therapeutic option to diminish the burden of breast cancer therapy.

Trial Registration

Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01536314","term_id":"NCT01536314"}}NCT01536314     

Ultrastructure of the presumed ion-transporting cells in the gills of ammocoete lampreys,Lampetra fluviatilis (L.) and Lampetra planeri (Bloch)

Summary Mitochondria-rich cells were located in the interplatelet area of gill filaments from ammocoete Lampetra fluviatilis and L. planeri. The ultrastructure of this cell type differs from typical teleost chloride cells by the absence of a tubular, smooth endoplasmic reticulum (SER). This difference is discussed in relation to the presumed functions of the cell and to the evolutionary histories of lampreys and teleosts. It is concluded that the mitochondria-rich cell is responsible for the active uptake of ions by the ammocoete gill.     

The distribution of mucous cells in the epidermis of the brown trout Salmo trutta (L.) and the char Salvelinus alpinus (L.)

The mucus of the trout and char was found to contain only one sialic acid, n-acetyl neuraminic acid (NANA). The concentration of NANA in the epidermis is directly proportional to the mucous cell concentration. In both species the highest concentration of mucous cells occurs on the anterior regions of the body and there are significantly fewer cells on the fins. These findings are discussed in the light of our knowledge of the functions of fish mucus.     

Redistribution of microtubules and pericentriolar material during the development of polarity in mouse blastomeres

The distribution of microtubules and microtubule organizing centers (MTOCs) during the development of cell polarity in eight-cell mouse blastomeres was studied by immunofluorescence and immunoelectron microscopy using monoclonal anti-tubulin antibodies and an anti-pericentriolar material (PCM) serum. In early eight-cell blastomeres microtubules were found mainly around the nucleus and in the cell cortex, whereas PCM foci were observed dispersed in the cytoplasm. During the eight-cell stage, microtubules disappeared from the area adjacent to the zone of intercellular contact and accumulated in the apical part of the cell while their number decreased in the basal domain. The PCM also relocalized to the apical domain of the cell, but this occurred after the redistribution of the microtubules by a mechanism that involved the microtubule network. The possible roles of both MTOCs and microtubules in establishing cell polarity are discussed.     

Crowding causes prolonged leucopenia in salmonid fish, despite interrenal acclimation

Crowding for 3 weeks significantly reduced the coefficient of condition of both brown trout and rainbow trout. However, acclimation of the hypothalamic-pituitary-interrenal (HPI) axis, as assessed by changes in plasma cortisol levels, occurred within 6 days for brown trout and within 10 days for rainbow trout. Blood lactate levels were significantly reduced in the crowded fish of both species throughout the experiment. Sexual maturation of the male fish significantly elevated the number of circulating red blood cells in both species, reduced the lactate levels in brown trout and elevated cortisol levels in the rainbow trout. Despite the relatively rapid interrenal acclimation, the numbers of thrombocytes and lymphocytes in the blood of both species were significantly reduced during the period of crowding and it is concluded that changes in the composition of circulating blood cells are more reliable indicators of chronic crowding stress than are plasma cortisol levels. These findings are discussed in relation to the role of the HPI axis in suppressing the defence systems of salmonid fish during periods of chronic stress.     

Determination of the phytotoxicity of barium in leach-field disposal of gas well brines

Summary A study was conducted to determine the effect of barium on yield and elemental composition of plants growing near natural gas wells. Brines containing potentially phytotoxic concentrations of barium are periodically released into leach-fields at these wells. Data on plant yield, soil and plant Ba, Ca, Mg, Na, and K concentrations, and soil pH were collected from high-barium well sites, and from greenhouse experiments using simulated brines. Barium had no detectable effect upon plant yield, and contributed only to variations in its own concentration in plants studied. Barium also exhibited biodiminution, in contrast to all other elements studied. Sodium was implicated at the major cause of phytotoxicity at gas well leach-fields. Due to interference of potassium uptake by soidum, the soil sodium/potassium ratio was found to be closely correlated with plant yield fluctuations.     

Analysis of the neurohypophyseal components accumulating in the supraoptic nucleus of the rat after injection of colchicine

[35S]Cysteine has been injected into the supraoptic nuclei of normal rats and of animals given 7 micrograms colchicine into the cerebrospinal fluid to inhibit transport of neurosecretory granules. Analysis of extracts of the supraoptic nuclei 20 min or 6 h after isotope injections showed that (i) colchicine does not affect biosynthesis, i.e., incorporation of tracer into the common precursors of neurohypophyseal hormones and their associated neurophysins, and (ii) processing of precursors inside the arrested granules proceeds normally.     

Ferulic acid: a substrate for two isoperoxidases from Nicotiana tabacum tissue cultures

An anodic isoperoxidase (A₂) from tobacco tissue culture W-38 and a cathodic isoperoxidase (C₄) from tobacco tissue suspension culture WR-132 have been separated and characterized. Both isoperoxidases catalysed oxidation of ferulic acid in the presence of H₂O₂. When the reaction mixture was subjected to TLC, ferulic acid was found to have been converted to an unknown compound which, after treatment with ammonia, fluoresces green in UV light. Both the isoperoxidases A₂ and C₄ appear to follow simple Michaelis-Menten kinetics with respect to guaiacol as the substrate. The Kms for guaiacol are 4 and 4·5 mM for isoperoxidases C₄ and A₂, respectively. The pH optimum for both enzymes is about 6·0. The effect of various phenolic and related compounds on the activity of each isoperoxidase is reported and discussed.