Ganglioside GM1 (porcine) ameliorates paclitaxel-induced neuropathy in rats.

BACKGROUND: Paclitaxel, an anti-neoplastic agent effective against several solid tumors, has several side effects including peripheral neuropathy. So far, there are no effective treatments for this complication. Monosialic acid ganglioside (GM1) has been shown to protect neurons against injuries and degeneration. However, its efficacy in the treatment of paclitaxel-induced neuropathy has not been verified. OBJECTIVE: To evaluate the effect of porcine GM1 on neurophysiological abnormalities in rats receiving paclitaxel. MATERIAL AND METHOD: Fifty-four Wistar rats were divided into control, vehicle for paclitaxel (Cremophor EL), paclitaxel, and paclitaxel + GM1 groups. Paclitaxel 16 mg/kg/week for five consecutive weeks was given intraperitoneally. Treatment with 30 mg/kg 5 days per week of GM1 was started 3 days prior to the first dose and continued until 3 days after the last dose of paclitaxel. Tail and hind paw thermal thresholds including tail motor nerve conduction velocity (MNCV) were measured prior to and after the start of treatments. Histopathology of the sciatic nerve was also examined. RESULTS: Paclitaxel alone induced thermal hypoalgesia and reduced tail MNCV Less severe abnormalities were also found with the vehicle. GM1 appeared to prevent the development of hypoalgesia and ameliorated the decreased MNCV without any evidence of Guillain-Barre Syndrome. Mild endoneurial edema and axonal degeneration in the sciatic nerve sections were seen in paclitaxel treated rats. Microtubule accumulation and activated Schwann cell were also presented in the paclitaxel treated groups. CONCLUSION: These data suggest that porcine GM1 may be useful in the prevention and treatment of paclitaxel-induced neuropathy. However the adverse effect of Cremophor EL should be of concern.

Tissue engineering of cartilage with porous polycarprolactone--alginate scaffold: the first report of tissue engineering in Thailand.

OBJECTIVE: To engineer human cartilage with porous polycaprolactone (PCL)-Alginate Scaffold. BACKGROUND: Polycaprolactone (PCL) is a prolonged degradable polymer that has good mechanical strength. The authors fabricated PCL as an ear shaped scaffold. Alginate hydrogel was used to seed chondrocyte into the PCL porous scaffold by a gel-cell seeding technique. MATERIAL AND METHOD: PCL Scaffolds were fabricated like human pinna by particle leaching technique. Chondrocyte was isolated from human rib cartilage and then cultured. The cultured chondrocyte were mixed with 1.2% alginate and b-FGF (basic-fibroblast growth factor) 5 ng/ml at a concentration of 25 x 10(6) cell/ml, then were seeded in porous PCL scaffold to make the constructs. The constructs were cultured in vitro for 1 week. Then they were implanted in subcutaneous plane of the back of six-female nude mice (5 weeks old). Two nude mice were sacrificed at 2, 3, and 6 months. Histological study was done (H&E, Alcian blue, collagen type II). RESULT: Neocartilage was formed in the porous cavity of PCL scaffold. At 2 and 3 months, neocartilage were similar to very young cartilage. At 6 months, they were mature. The delayed maturation until 6 months and the highly vascularization of neocartilage in the early phase was the effect of human b-FGF The growths of neocartilage islands in porous cavity were also observed along with degradation ofPCL inter-porous septum. CONCLUSION: This paper reports the first success of cartilage tissue engineering in Thailand.

Clinical, pathological, and electron microscopic findings in two Thai children with Pompe disease.

The authors report on a Thai boy who first presented at age 7 months and an unrelated Thai girl in her neonatal period with hypotonia, cardiomegaly and hepatomegaly. Their chest roentgenograms showed markedly enlarged hearts, EKGs showed abnormally shortened PR intervals with gigantic QRS complexes, and electron microscopic studies of their skin samples showed glycogen accumulations surrounded by membranes. The boy died at age 22 months and the girl at age 9 months due mainly to cardiorespiratory failure. Autopsy of the girl showed marked accumulation of glycogen in the liver, heart and numerous additional tissues including her brain. The clinical, pathological, and electron microscopic findings of these two children are consistent with the diagnosis of Pompe disease. Pompe disease is an autosomal recessive disorder of glycogen metabolism resulting from deficiencies in activity of the lysosomal acid alpha-glucosidase. Definite diagnosis of the disease can be made from a biochemical test or a mutation analysis. To the authors' knowledge, no service laboratories in Thailand offer the tests. Because Thai children have occasionally been reported to be affected by Pompe disease, an attempt to establish a definite diagnostic test for Pompe disease in Thailand should be encouraged. With a definite diagnosis, the proper genetic counseling and prenatal diagnosis could be offered to the families.