Characterization of neurotoxic effects of NMDA and the novel neuroprotection by phytopolyphenols in mice.

Excitotoxicity plays a major role in various neurological disorders. In this study, we explored the behavioral and neurotoxic effects of intraventricular NMDA administration in mice. After NMDA injection, acute seizures were followed by impairments in locomotor activity, motor performance on a rotarod, and climbing ability. Mice killed 1 day after NMDA administration showed increased synaptosomal reactive oxygen species ROS production and calcium concentration and decreased mitochondrial membrane potential, mitochondrial reductase activities, and neuronal membrane Na+, K+ -ATPase and mg2+ -ATPase activities. One and 3 days after excitotoxic injury, Golgi stains showed that dendritic length and spine density were significantly decreased in neurons of the hippocampal dentate gyrus. Some mice received honokiol, tea polyphenol plus memantine, and honokiol plus memantine prior to NMDA treatment; the occurrence of generalized seizures was attenuated, seizure scores were reduced, latency to generalized seizures was prolonged, and motor impairments were lessened. Moreover, all of the neurochemical changes of the synaptosomes were also ameliorated. In conclusion, the behavioral and neurotoxic effects of intracerebroventricular injection of NMDA were ameliorated by treatment with honokiol alone or combined treatment with either tea polyphenol plus memantine or honokiol plus memantine, but only partly by either tea polyphenol or memantine alone. The therapeutic potential of these neuroprotective regimens in treating excitotoxicity-related diseases merits for further investigation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Mechanisms of hypolipidemic and anti-obesity effects of tea and tea polyphenols

Among the health-promoting effects of tea and tea polyphenols, the cancer-chemopreventive effects in various animal model systems have been intensively investigated; meanwhile, the hypolipidemic and antiobesity effects in animals and humans have also become a hot issue for molecular nutrition and food research. It has been demonstrated that the body weights of rats and their plasma triglyceride, cholesterol, and LDL-cholesterol have been significantly reduced by feedings of oolong, black, pu-erh, and green tea leaves to the animals. It has been suggested that the inhibition of growth and suppression of lipogenesis in MCF-7 breast cancer cells may be through down-regulation of fatty acid synthase gene expression in the nucleus and stimulation of cell energy expenditure in the mitochondria. The experimental data indicated that the molecular mechanisms of fatty acid synthase gene suppression by tea polyphenols (EGCG, theaflavins) may invite down-regulation of EGFR/PI3K/Akt/Sp-1 signal transduction pathways.     

Potentiation of miniature endplate potential frequency by ATP in Xenopus tadpoles

1. Extracellular application of ATP (1 mM), a substance co-stored and co-released with acetylcholine in peripheral nervous systems, potentiated the spontaneous secretion of acetylcholine (ACh) but had no effect on the amplitude and decay time constant of miniature endplate potentials (m.e.p.ps) at neuromuscular synapses in Xenopus tadpoles. 2. alpha,beta-Methylene ATP (0.3 mM) and GTP (1 mM) were also effective in increasing m.e.p.p. frequency. On the other hand, ADP, AMP and adenosine (all at 1 mM) decreased m.e.p.p. frequency. 3. Unlike the transient effect of ATP analogue and GTP on m.e.p.p. frequency, the phorbol ester TPA (2 microM) which is a protein kinase C activator, increased m.e.p.p. frequency consistently and the effects lasted as long as the presence of TPA. 4. Staurosporine (0.5 microM) and H-7 (10 microM), which are protein kinase C inhibitors, each decreased the basal level of m.e.p.p. frequency and markedly inhibited the effects of both ATP and TPA. 5. These results suggest that there is a basal activity of cytosolic protein kinases in the nerve terminals of Xenopus tadpoles and the effect of ATP is probably mediated by the binding of membrane surface purinoceptors which in turn activates cytosolic protein kinases and increases ACh release.     

Studies on the neuromuscular blocking action of commercial paraquat in mouse phrenic nerve-diaphragm

The neuromuscular blocking actions of commercial and pure paraquat on the mouse phrenic nerve-diaphragm were compared. Twitch responses of mouse diaphragm to nerve stimulation were inhibited by commercial paraquat (5-500 microM), but not by pure paraquat (1 mM). At concentrations greater than 30 microM, commercial paraquat also directly inhibited the contractions induced by electrical stimulation of the muscle. The inhibitory actions of commercial paraquat on twitches were potentiated by pretreatment with either 0.7 microM d-tubocurarine or 2.2 microM succinylcholine. Moreover, commercial paraquat inhibited acetylcholine contracture of the denervated mouse diaphragm. Similar to d-tubocurarine, commercial paraquat protected the diaphragms from inhibition by alpha-bungarotoxin and also inhibit the binding [125I]-alpha-bungarotoxin. Electrophysiological studies revealed that commercial paraquat inhibited the amplitude of miniature end-plate potentials (m.e.p.ps) and end-plate potentials (e.p.ps) of mouse diaphragm. The inhibition induced by commercial paraquat was frequency-dependent. All of these findings indicate that commercial paraquat possesses curare-like actions and inhibits muscle contractions by binding to the postsynaptic nicotinic acetylcholine receptors. Pure paraquat does not have these effects. Analysis of the components in commercial paraquat suggested that paraquat by-products and the added emulsifying agent were responsible for these observations. The clinical significance of these findings is that this neuromuscular blocking may contribute to the respiratory failure in paraquat intoxicated patients.     

Morphological changes induced by prostaglandin E in cultured rat osteoblasts

OBJECTIVES: We estimated the risk of sudden cardiac death (SCD), from a spontaneous episode of ventricular arrhythmia (VT/VF), after a successful surgical myocardial revascularization (coronary artery bypass grafting; CABG) procedure. Predictors of these events were identified, and long term benefits of the prophylactic regimes, that were used to control these events, were evaluated. METHODS: We selected 8642 consecutive patients, who had undergone an isolated and first time CABG procedure, between 1/3/1980 and 1/3/1995. A standard hazard function model (1) was used for statistical analysis. Efficacy of the prophylactic regimes, was examined in a group of 350 high risk patients, with a preoperative left ventricular ejection fraction 30% or less, who were recently operated since 1/1/1988. Electrophysiologic (EP) guided prophylaxis was used in 92 (26%) patients, who had survived a documented episode of SCD, and remaining 258 patients were maintained on antiarrhythmic medication on an empirical basis. A sequential EP evaluation was performed, when indicated. RESULTS: During an early phase of hazard, which mainly lasted for up to 3 months after CABG, incremental risk factors were preoperative LVEF 30% or less (P = 0.0007) and preoperative episodes of VT/VF (P = 0.04). This phase was followed by a constant phase with a low risk of the events, which merged into a slowly rising late phase after 6 years. EP guided prophylaxis, reduced the risk of SCD in high risk patients (P = 0.03). A sequential EP evaluation, helped to detect the problems of drug resistance and a cross over from non-sustained to sustained runs of VT/VF. CONCLUSIONS: Despite a successful CABG surgery, risk of VT/VF persists. A routine EP evaluation before and after a CABG procedure is recommended in all patients with a poor left ventricular function.     

Phorbol ester-induced contractions of mouse detrusor muscle are inhibited by nifedipine

BACKGROUND: There are many conditions related to brain abscess. Brain abscesses resulting from nasopharyngeal carcinoma is rare. It is unusual for an intracranial abscess to appear as the initial clinical presentation of nasopharyngeal carcinoma. CASE REPORT: A 43-year-old male patient suffering from nasopharyngeal carcinoma with the initial manifestation of an intracranial abscess without symptoms and signs suggestive of the primary nasopharyngeal carcinoma is reported. The diagnosis was particularly elusive and was not made until the third admission. CONCLUSION: Although it is rare, intracranial abscess should be considered as one of the possible manifestations of nasopharyngeal carcinoma.