Antinociceptive efficacy of lacosamide in the monosodium iodoacetate rat model for osteoarthritis pain

The etiology of osteoarthritis is multifactorial, with inflammatory, metabolic, and mechanical causes. Pain in osteoarthritis is initiated by mild intra-articular inflammation and degeneration of articular cartilage and subchondral bone. The principle of treatment with acetaminophen or non-steroidal anti-inflammatory drugs is to reduce pain and improve joint function. Recently, animal models for osteoarthritic pain behavior have been established. The most frequently used rat model for analyzing properties of drugs on the pathology of osteoarthritis is the injection of the metabolic inhibitor monosodium iodoacetate into the joint, which inhibits the activity of glyceraldehyde-3-phosphate dehydrogenase in chondrocytes. Here, we characterize the effect on pain behavior of lacosamide, a member of a family of functionalized amino acids that are analogues of endogenous amino acids and D-serine, in the monosodium iodoacetate rat model for osteoarthritis in comparison to diclofenac and morphine. Lacosamide (3, 10, and 30 mg/kg) was able to reduce secondary mechanical allodynia and hyperalgesia similarly to morphine (3 mg/kg). In contrast, diclofenac (30 mg/kg) was only effective in reducing secondary mechanical hyperalgesia. During the first week, pain is induced mainly by inflammation in the iodoacetate model, but afterwards inflammation plays only a minor role in pain. Lacosamide was able to inhibit pain at days 3, 7 and 14 after induction of arthritis. This shows that lacosamide is able to reduce pain behavior induced by multiple mechanisms in animals

In vitro and in vivo gene therapy with CMV vector-mediated presumed dog β-nerve growth factor in pyridoxine-induced neuropathy dogs

Due to the therapeutic potential of gene therapy for neuronal injury, many studies of neurotrophic factors, vectors, and animal models have been performed. The presumed dog β-nerve growth factor (pdβ-NGF) was generated and cloned and its expression was confirmed in CHO cells. The recombinant pdβ-NGF protein reacted with a human β-NGF antibody and showed bioactivity in PC12 cells. The pdβ-NGF was shown to have similar bioactivity to the dog β-NGF. The recombinant pdβ-NGF plasmid was administrated into the intrathecal space in the gene therapy group. Twenty-four hours after the vector inoculation, the gene therapy group and the positive control group were intoxicated with excess pyridoxine for seven days. Each morning throughout the test period, the dogs' body weight was taken and postural reaction assessments were made. Electrophysiological recordings were performed twice, once before the experiment and once after the test period. After the experimental period, histological analysis was performed. Dogs in the gene therapy group had no weight change and were normal in postural reaction assessments. Electrophysiological recordings were also normal for the gene therapy group. Histological analysis showed that neither the axons nor the myelin of the dorsal funiculus of L4 were severely damaged in the gene therapy group. In addition, the dorsal root ganglia of L4 and the peripheral nerves (sciatic nerve) did not experience severe degenerative changes in the gene therapy group. This study is the first to show the protective effect of NGF gene therapy in a dog model

Small

Bioenergetic deficits are known to be significant contributors to neurodegenerative diseases. Nevertheless, identifying safe and effective means to address intracellular bioenergetic deficits remains a significant challenge. This work provides mechanistic insights into the energy metabolism-regulating function of colloidal Au nanocrystals, referred to as CNM-Au8, that are synthesized electrochemically in the absence of surface-capping organic ligands. When neurons are subjected to excitotoxic stressors or toxic peptides, treatment of neurons with CNM-Au8 results in dose-dependent neuronal survival and neurite network preservation across multiple neuronal subtypes. CNM-Au8 efficiently catalyzes the conversion of an energetic cofactor, nicotinamide adenine dinucleotide hydride (NADH), into its oxidized counterpart (NAD ), which promotes bioenergy production by regulating the intracellular level of adenosine triphosphate. Detailed kinetic measurements reveal that CNM-Au8-catalyzed NADH oxidation obeys Michaelis-Menten kinetics and exhibits pH-dependent kinetic profiles. Photoexcited charge carriers and photothermal effect, which result from optical excitations and decay of the plasmonic electron oscillations or the interband electronic transitions in CNM-Au8, are further harnessed as unique leverages to modulate reaction kinetics. As exemplified by this work, Au nanocrystals with deliberately tailored structures and surfactant-free clean surfaces hold great promise for developing next-generation therapeutic agents for neurodegenerative diseases

Concomitant differentiation of a population of mouse embryonic stem cells into neuron‐like cells and schwann cell–like cells in a slow‐flow microfluidic device

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135245/1/dvdy24466_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135245/2/dvdy24466.pd

Validation de trois nouveaux modèles animaux de maladies neurologiques humaines et réflexions sur la modélisation

STRASBOURG-Sc. et Techniques (674822102) / SudocSudocFranceF

Effect of lacosamide and morphine on mechanical hyperalgesia after monosodium iodoacetate (MIA) injection

<p><b>Copyright information:</b></p><p>Taken from "Antinociceptive efficacy of lacosamide in the monosodium iodoacetate rat model for osteoarthritis pain"</p><p>http://arthritis-research.com/content/9/1/R14</p><p>Arthritis Research & Therapy 2007;9(1):R14-R14.</p><p>Published online 6 Feb 2007</p><p>PMCID:PMC1860073.</p><p></p> Effect of lacosamide and morphine on paw withdrawal threshold in the paw pressure test in MIA-treated animals on day 3, day 7 and day 14 after arthritis induction. Rats were tested 45 to 60 minutes post-drug. Data from 12 animals/group are presented as mean ± SEM. *< 0.05 Dunnett's test versus MIA/vehicle treated animals

Tactile allodynia measurement in normal rats after lacosamide treatment

<p><b>Copyright information:</b></p><p>Taken from "Antinociceptive efficacy of lacosamide in the monosodium iodoacetate rat model for osteoarthritis pain"</p><p>http://arthritis-research.com/content/9/1/R14</p><p>Arthritis Research & Therapy 2007;9(1):R14-R14.</p><p>Published online 6 Feb 2007</p><p>PMCID:PMC1860073.</p><p></p> Effect of lacosamide on paw withdrawal threshold in the von Frey filament test in saline treated normal rats. Rats were tested 30 minutes post-drug. Data from eight animals/group are presented as mean ± SEM

Effect of diclofenac on mechanical hyperalgesia after monosodium iodoacetate (MIA) injection

<p><b>Copyright information:</b></p><p>Taken from "Antinociceptive efficacy of lacosamide in the monosodium iodoacetate rat model for osteoarthritis pain"</p><p>Arthritis Research & Therapy 2007;9(1):R14-R14.</p><p>Published online 6 Feb 2007</p><p>PMCID:PMC1860073.</p><p></p> Effect of diclofenac on paw withdrawal threshold in the paw pressure test in MIA-treated animals on days 3, 7 and 14 after arthritis induction. Rats were tested 45 to 60 minutes post-drug. Data from 12 animals/group are presented as mean ± SEM. *< 0.05 Dunnett's test versus MIA/vehicle treated animals

Searching for Mediterranean bath sponges (Demospongiae: Dictyoceratida: Spongiidae) in the Northeast Atlantic reveals a new species: an integrative taxonomic approach

Abstract Bath sponges, included in the Spongiidae (Demospongiae: Dictyoceratida), are distributed across the oceans of the world, with a greater abundance in temperate, subtropical, and tropical zones. Their harvest started during ancient times in the Mediterranean Sea, which shed light on the whole family. Most of the Mediterranean Spongiidae have been reported repeatedly from the Northeast Atlantic, notably along the Iberian peninsula. The aim of this study was to clarify the taxonomic status of these sponges after a recent sampling effort in the French Pays Basque and the Spanish Cantabria, complemented by several Mediterranean Sea stations, including the Strait of Gibraltar. An integrative taxonomic approach was adopted for the first time on a set of Spongiidae samples from the Northeast Atlantic, assessing the congruence of analyses of: (i) the morphology of the spongin skeleton; (ii) two different parts of the genome (mitochondrial and nuclear); and (iii) metabolomic fingerprints, to delimit the frontiers between species better. A new bath sponge species is described herein, and significant advances and changes are proposed for the systematics of the family