Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A case of toxic leucoencephalopathy induced by 5 FU derivatives is reported. A 46-year-old woman was diagnosed as having breast cancer, and radical mastectomy was performed on May, 1982. After operation, she was given irradiation and 5FU derivative (tegafur or carmofur) 600 mg and Nolvadex 20 mg (tamoxifen citrate) were administered every day. After taking the medication for a month, she began to stagger and developed a tremor in both arms. She was admitted to our hospital on August 16, because she showed evidence of dysarthria and memory disturbance in addition to her initial complaints. Soon after admission, she developed akinetic mutism, and metastasis in the brain stem was suspected. In spite of her severe condition, she was given radiation over the posterior fossa and continued the medication. On September 22, CT disclosed low density area in the centrum semiovale bilaterally. She died of DIC on November 30. An autopsy was performed. The brain weight was 1110 g and the outer surface of the brain was normal. In frontal cut surfaces stained with K.B., bilateral degeneration of the centrum semiovale was apparent. Microscopically, the degree of myelin degeneration was stronger than that of axon, and numerous fatty granular cells were found in the degenerated area. There were no bizarre shaped astrocytes, inclusion body or cellular infiltration. Fibrillary gliosis was scanty. No metastasis was found in the central nervous system or other organs. Based on these pathological findings and clinical history, toxic leucoencephalopathy induced by 5 FU derivatives was suggested.
 ...
PMID:[A case of toxic leucoencephalopathy induced by 5FU derivatives]. 393 66

Convection-enhanced delivery (CED) permits the homogeneous distribution of therapeutic agents throughout localized regions of the brain parenchyma without causing tissue damage as occurs with bolus injection. Here, we examined whether CED infusion of the N-type calcium channel antagonists omega-conotoxin GVIA (omega-CTX-G) and omega-conotoxin MVIIA (omega-CTX-M) can attenuate kindling measures in fully amygdala-kindled rats. Rats were implanted with a combination infusion cannula-stimulating electrode assembly into the right basolateral amygdala. Fully kindled animals received infusions of vehicle, omega-CTX-G (0.005, 0.05, and 0.5 nmol), omega-CTX-M (0.05, 0.15, and 0.5 nmol), proteolytically inactivated omega-CTX-M (0.5 nmol), or carbamazepine (500 nmol) into the stimulation site. CED of omega-CTX-G and omega-CTX-M over a 20-min period resulted in a dose-dependent increase in the afterdischarge threshold and a decrease in the afterdischarge duration and behavioral seizure score and duration during a period of 20 min to 1 week after the infusion, indicating an inhibitory effect on the triggering and expression of kindled seizures. The protective effects of omega-conotoxins reached a maximum at 48 h postinfusion, and then they gradually resolved over the next 5 days. In contrast, carbamazepine was active at 20 min but not at 24 h after the infusion, whereas CED of vehicle or inactivated omega-CTX-M had no effect. Except for transient tremor in some rats receiving the highest toxin doses, no adverse effects were observed. These results indicate that local CED of high-molecular-weight presynaptic N-type calcium channel blockers can produce long-lasting inhibition of brain excitability and that they may provide prolonged seizure protection in focal seizure disorders.
 ...
PMID:Prolonged attenuation of amygdala-kindled seizure measures in rats by convection-enhanced delivery of the N-type calcium channel antagonists omega-conotoxin GVIA and omega-conotoxin MVIIA. 1771 91

Electrical stimulation of sub-cortical brain regions (the basal ganglia), known as deep brain stimulation (DBS), is an effective treatment for Parkinson's disease (PD). Chronic high frequency (HF) DBS in the subthalamic nucleus (STN) or globus pallidus interna (GPi) reduces motor symptoms including bradykinesia and tremor in patients with PD, but the therapeutic mechanisms of DBS are not fully understood. We developed a biophysical network model comprising of the closed loop cortical-basal ganglia-thalamus circuit representing the healthy and parkinsonian rat brain. The network properties of the model were validated by comparing responses evoked in basal ganglia (BG) nuclei by cortical (CTX) stimulation to published experimental results. A key emergent property of the model was generation of low-frequency network oscillations. Consistent with their putative pathological role, low-frequency oscillations in model BG neurons were exaggerated in the parkinsonian state compared to the healthy condition. We used the model to quantify the effectiveness of STN DBS at different frequencies in suppressing low-frequency oscillatory activity in GPi. Frequencies less than 40 Hz were ineffective, low-frequency oscillatory power decreased gradually for frequencies between 50 Hz and 130 Hz, and saturated at frequencies higher than 150 Hz. HF STN DBS suppressed pathological oscillations in GPe/GPi both by exciting and inhibiting the firing in GPe/GPi neurons, and the number of GPe/GPi neurons influenced was greater for HF stimulation than low-frequency stimulation. Similar to the frequency dependent suppression of pathological oscillations, STN DBS also normalized the abnormal GPi spiking activity evoked by CTX stimulation in a frequency dependent fashion with HF being the most effective. Therefore, therapeutic HF STN DBS effectively suppresses pathological activity by influencing the activity of a greater proportion of neurons in the output nucleus of the BG.
 ...
PMID:A biophysical model of the cortex-basal ganglia-thalamus network in the 6-OHDA lesioned rat model of Parkinson's disease. 2686 34