Newsletter # 23
Animal models
NEUROFIT offers a long list of in vivo and in vitro validated methods and disease models for drug screening.
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NEUROFIT offers on fee-for-service basis the quantification IENF in rat skin biopsies as a robust and cost-effective assay to evaluate:
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Black arrows indicate IENF
White arrowheads indicate dermal nerve bundles -
NEUROFIT offers on fee-for-service basis the quantification IENF in rat skin biopsies as a robust and cost-effective assay to evaluate:
the peripheral neuropathy as a result of a potential side-effect of a drug treatment (safety profiling of drug candidates) the neuroprotective effect of drug therapy as a treatment for peripheral neuropathy (preclinical efficacy testing) See examples of NEUROFIT data regarding the :
Diabetic neuropathy Paclitaxel-related neuropathy Dideoxycytidine-related neuropathy
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Many drugs and toxins have been reported to induce peripheral neuropathies. Often, this adverse effect requires the withdrawal of the treatment.
Example of drugs: Chemotherapy agents (Paclitaxel, Vincristine, Cisplatin ...) Anti-HIV therapy (Nucleoside analog reverse transcriptase inhibitors) Antibiotic (Metronidazole)
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Degeneration of intraepidermal nerve fibers (IENF) is also found in neuropathies associated with metabolic (diabetes), infectious (HIV/AIDS) and autoimmune (vasculitis) diseases.
Degeneration of IENF is a sensitive clinical marker to evaluate the severity of peripheral neuropathies. Loss of IENF is observed in both symptomatic or asymptomatic peripheral neuropathies.
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Diabetic neuropathy Groups Mean sem n Non-diabetic rats 75.667 2.014 5 Diabetic rats (day 21 post-STZ) 44.708 6.161 5 Diabetic rats (day 41 post-STZ) 15.552 0.857 4
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Paclitaxel-related neuropathy
Dideoxycytidine-related neuropathyDrugs Rat strain Treatment regimen Timepoints IENF density (n/mm) sem n p-value (t-test) Placebo (Saline) Dideoxycytidine (50 mg/kg; i.v.) Sprague-Dawley
Sprague-Dawley1 single i.v Day 8
Day 880.4
56.02.1
46
5
0.01Placebo (Saline) Paclitaxel (2 mg/kg; i.p.) Sprague-Dawley
Sprague-Dawley4 injections every other day Day 31
Day 3176.03
58.71
73
5
0.0202
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