RESUMEN
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.
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Antineoplásicos Fitogénicos/toxicidad , Gangliósido G(M1)/farmacología , Paclitaxel/toxicidad , Enfermedades del Sistema Nervioso Periférico/tratamiento farmacológico , Animales , Relación Dosis-Respuesta a Droga , Gangliósido G(M1)/efectos adversos , Síndromes de Neurotoxicidad/tratamiento farmacológico , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Ratas , Ratas Wistar , Sensación/efectos de los fármacosRESUMEN
BACKGROUND: The attack of migraine has been observed to be associated with low level of serotonin (5-HT). Although the mechanism underlying this relationship is still unclear, change in cortical excitability or susceptibility of trigeminal system is a possible explanation. OBJECTIVES: The aim was to study the effect of 5-HT depletion on the development of cortical spreading depression (CSD) and CSD-evoked trigeminal nociception. METHODS: Wistar rats were separated into low 5-HT and control groups (eight rats each). 5-HT was depleted by administration of para-chlorophenylalanine, a tryptophan hydroxylase inhibitor. CSD was induced by applying 3 mg of potassium chloride on parietal cortex. Cortical activity was monitored for 1 hour. Trigeminal nociception was determined using number of Fos-immunoreactive (Fos-IR) neurons in trigeminal nucleus caudalis as the indicator. RESULTS: Application of KCl led to the development of series of depolarization shift characteristics for CSD. The development of these CSD waves was enhanced in low 5-HT state. The area under curve of each CSD wave and the number of CSD waves occurring within 1 hour were greater in low 5-HT group. No significant change in peak amplitude and duration of CSD wave was observed. The numbers of Fos-IR cells on ipsilateral and contralateral trigeminal nucleus caudalis were significantly greater in the low 5-HT group than those of the controls. CONCLUSION: Our findings indicate that 5-HT depletion enhances CSD-induced trigeminal nociception by increasing the cortical excitability and sensitivity of trigeminal nociceptive system. These findings may provide a better understanding regarding the relationship between low 5-HT and clinical headaches.
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Depresión de Propagación Cortical/fisiología , Dolor/fisiopatología , Serotonina/fisiología , Nervio Trigémino/fisiopatología , Animales , Electroencefalografía , Electrofisiología , Genes fos/genética , Masculino , Ratas , Ratas WistarRESUMEN
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.
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Alginatos/farmacología , Cartílago/metabolismo , Condrocitos/citología , Poliésteres/farmacología , Ingeniería de Tejidos/métodos , Alginatos/metabolismo , Animales , Células Cultivadas , Femenino , Ratones , Ratones Desnudos , Poliésteres/metabolismo , Porosidad , TailandiaRESUMEN
INTRODUCTION: Pompe disease is one of the lysosomal storage disorders caused by alpha-glucosidase deficiency. The disease is characterized by accumulation of glycogen in the lysosome. The accumulation has unique ultrastructural features, which enable a prenatal diagnosis possible by electron microscopy. MATERIALS AND METHODS: A prenatal diagnosis of Pompe disease by electron microscopic study of chorionic villus biopsies is described in a fetus of a mother whose previous child had died of the disease. RESULTS: Electron microscopy revealed fibrocytes with typical vacuoles filled with glycogen. A prenatal diagnosis of Pompe disease was made and subsequently confirmed by the autopsy study of the abortus. CONCLUSION: We report the usefulness of electron microscopy for prenatal diagnosis in the first trimester of Pompe disease.
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Muestra de la Vellosidad Coriónica , Vellosidades Coriónicas/ultraestructura , Enfermedad del Almacenamiento de Glucógeno Tipo II/diagnóstico , Microscopía Electrónica/métodos , Aborto Inducido , Adulto , Femenino , Enfermedad del Almacenamiento de Glucógeno Tipo II/metabolismo , Humanos , Masculino , EmbarazoRESUMEN
This study investigated whether perivascular inflammation is necessary in the process of cortical spreading depression (CSD)-induced trigeminovascular nociception. CSD was induced by application of potassium chloride on rat parietal surface. Cortical microcirculation was studied using intravital fluorescent videomicroscopy, laser Doppler flowmetry and electron microscopy. Trigeminal nociception was determined using Fos immunoreactivity as the indicator. We found that KCl application caused cyclic cortical hyperaemia and pial microvascular dilation. Neither increased leukocyte-endothelial adhesion nor extravasation of macromolecule was demonstrated. Ultrastructural study revealed increased endothelial pinocytosis but tight junction remained intact. Despite no intense perivascular inflammation, we observed significantly increased Fos-immunoreactivity in trigeminal nucleus caudalis. These results suggest that perivascular inflammation is not necessary in the process of CSD-evoked trigeminovascular nociception.
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Depresión de Propagación Cortical/fisiología , Meningitis/fisiopatología , Nociceptores/fisiología , Núcleos del Trigémino/fisiología , Animales , Circulación Cerebrovascular/efectos de los fármacos , Craneotomía/métodos , Células Endoteliales/fisiología , Células Endoteliales/ultraestructura , Inmunohistoquímica/métodos , Flujometría por Láser-Doppler/métodos , Masculino , Microscopía Electrónica/métodos , Microscopía por Video/métodos , Nociceptores/efectos de los fármacos , Proteínas Oncogénicas v-fos/metabolismo , Cloruro de Potasio/farmacología , Ratas , Ratas Wistar , Factores de Tiempo , Núcleos del Trigémino/efectos de los fármacosRESUMEN
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.