tretinoin and Peripheral-Nervous-System-Diseases

In humans, exposure to organic solvents (OS) is frequent in work activities or as a recreational inhalant, inducing severe neuropathy (secondary to demyelization of peripheral nerves). We have previously shown that all-trans retinoic acid (ATRA) increases local content of neural growth factor (NGF), improving peripheral neuropathy of diverse origins. In this study, we evaluated the effect of ATRA on OS-induced peripheral neuropathy in experimental mice. Two simultaneous experiments were performed. The first one aimed to evaluate ATRA for the prevention of damage induced by OS, the second to test ATRA as an OS-induced neuropathy treatment. Nociceptive threshold latency and NGF concentration in serum and in peripheral nerves were determined. Morphological changes and evidence of sciatic nerve regeneration were evaluated. Mice exposed to OS developed neuropathy and axonal degeneration. ATRA diminished the effects of OS inhalation on sensorial changes and nerve morphology. Treatment with ATRA reversed sensorial and nerve morphological changes of OS-induced neuropathy, and this was associated with increased contents of NGF. Similar to previous experiences on diabetic and toxic neuropathy, ATRA reduced and partially reversed the peripheral neuropathy caused by OS exposure. These favorable effects apparently are due to local production of NGF induced by neural regeneration in response to the administration of retinoic acid.

Topics: Animals; Mice; Nerve Growth Factor; Nerve Regeneration; Pain Threshold; Peripheral Nervous System Diseases; Sciatic Nerve; Solvents; Tretinoin

Topics: Acne Vulgaris; Administration, Topical; Adolescent; Humans; Keratolytic Agents; Male; Peripheral Nervous System Diseases; Treatment Outcome; Tretinoin

Peripheral nervous system alterations were induced in adult rats by administration of cisplatin (CDDP) 2 mg/kg twice weekly for 4.5 weeks. Dorsal root ganglion neurons showed pathological changes. Morphometric determinations demonstrated a reduction in size of the somatic, nuclear and nucleolar area. The nucleoli were the most involved subcellular structures. Nerve conduction velocity and the tail-flick test for pain were both significantly altered in CDDP treated rats, whereas the rota-rod test for coordination revealed no changes in either treated or control rats. Analytical determinations demonstrated platinum accumulation in the DRG of CDDP treated rats. Spontaneous recovery, demonstrated by morphometric, electrophysiological, functional and analytical determinations, occurred after treatment discontinuation within about 7 weeks. A pilot study of the possible neuroprotective action of retinoic acid (RA) was also performed with this model of cisplatin neuronopathy. The rationale for using RA was based on its assumed antioxidant and neurotrophic effect. However, RA failed to prevent morphometric, electrophysiological, functional and analytical alterations induced by CDDP on DRG neurons. RA induced only a mild generalized protective effect.

Topics: Animals; Body Weight; Cisplatin; Female; Ganglia, Spinal; Injections, Intraperitoneal; Neural Conduction; Peripheral Nervous System Diseases; Random Allocation; Rats; Rats, Wistar; Tail; Tretinoin

Monoclonal IgM associated with a peripheral neuropathy often feature an antibody activity directed against the myelin-associated-glycoprotein. The main characteristics of the structure of these IgM are reviewed: the variable gene repertoire used by these antibodies is rather large. The VH genes belong to the different variability subgroups; this also holds true for the VL repertoire although the single V kappa 4 gene may be used quite often. These variable segments often exhibit somatic mutations clustered in the CDR regions suggesting an antigen driven process. The monoclonal IgM is produced by a B cell clone which may be undetectable in the majority of patients. Nevertheless, it is possible to detect clonal B cells in the blood which have the remarkable capacity to differentiate spontaneously in vitro to plasma cells. This process is dependent upon an IL6-autocrine differentiation pathway which may be modulated by some drugs such as interferons or all trans retinoic acid.

Topics: Antibodies, Monoclonal; B-Lymphocytes; Cell Differentiation; Humans; Immunoglobulin M; Interferons; Peripheral Nervous System Diseases; Plasma Cells; Tretinoin; Waldenstrom Macroglobulinemia