The Effect of Coriaria Lactone on NMDA Receptor Mediated Currents in Rat Hippocampal CA1 Neurons

Summary: To investigate the exact mechanism of epileptogenesis induced by coriaria lactone (CL), the effect of CL on NMDA receptor mediated current (IAsp) in rat hippocampal CA1 neu- rons was investigated by using nystatin perforated whole-cell patch clamp. 10-6-10-4 mol/L Asp acted on NMDA receptors and elicited an inward current (IAsp) at a holding potential (VH) of -40 mV in presence of 10-6 mol/L glycine and absence of Mg2+ extracellularly. CL enhanced NMDA receptor mediated current induced by Asp, but had no effect on threshold concentration, EC50, Hill coefficient as well as maximal-effect concentration and reversal potential of IAsp. The effect had no relationship with holding potential. These results showed that CL could enhance NMDA receptor mediated current to increase [Ca2+]i of neurons by acting on Gly site, thereby inducing epilepsy.

A Persistent Na⁺Current and Its Contribution to Burst-Like Firing in Ventral Tegmental Area Dopamine Neurons

The ventral tegmental area dopamine (DA VTA) neurons have the spontaneous tonic activity and an alteration of firing pattern from tonic to burst accelerates dopamine transmission more effectively in the mesoaccumbal dopaminergic system, leading to the reinforcing process of drugs of abuse such as alcohol and nicotine. In the present study, we examined whether a persistent Na+ current would contribute to burst firing in DA VTA neuronsusing nystatin-perforated recording. Tetrodotoxin (TTX) (1 μM) or riluzole (10 μM) hyperpolarized the membrane potential and stopped spontaneous firing of DA VTA neurons. In voltage-clamp analysis, a TTX and riluzole-sensitive and persistent Na+ current was activated at ?60 mV and reached maximal amplitude at ?40 mV. This persistent Na+ current was potentiated by a negative shift of the voltage of activation by eliminating Ca2+ from the extracellular solution. The Ca2+-free extracellular solution depolarized the membrane potential and increased the firing frequency of DA VTA neurons. When a continuous hyperpolarizing current was injected, the firing pattern of the DA VTA neurons transformed into burst-like firing;with average spike number of 4.9, average inter-spike interval of 221 ms, and an average plateau potential, on which the train of spikes generated, was 11 mV. The burst-like firing of DA VTA neurons was abolished by 10 μM riluzole. The concurrent blockade of both T-type Ca2+ current and small conductance Ca2+-activated K+(SK) currents by 100 μM nickel did not induce burst-like firing with or without continuous hyperpolarizing current injection in DA VTA neurons. In conclusion, increases in a persistent Na+ current that mediates a depolarizing driving force by removing extracellular Ca2+ contributes to burst-like firing in DA VTA neurons.

Nystatin-Neomycin-Polymyxin B Combination:Efficacy and Tolerance as 1st-Line Local Treatment of Infectious Vaginitis

Objective: To evaluate the efficacy and tolerance of a local treatment combining two antibacterials and one antifungal in patients with a clinical presentation suggesting infectious vaginitis. Patients and methods: 169 patients presenting with clinical criteria for vaginitis were included in an open, multicenter trial. Vaginal samples were taken for microbiological analyses and a triple-combination product of nystatin, neomycin and polymyxin B was then started as local treatment, without waiting for the test results. The treatment was continued with the usual dosage (1 vaginal capsule at bedtime for 12 days) for vaginal infections in the scope of the combination product with approved labeling. A second vaginal sample was performed at the end of the treatment. The main efficacy criterion was the clinical success rate (cure or improvement of the clinical signs and symptoms) according to the investigator.Results: 93 patients were included in the efficacy population. Non-exclusively fungal vaginitis (strictly bacterial or bacterial + fungal) represented 31.2% of the cases. The clinical success rate was 97.8% according to the investigator and 95.7% according to the patients. The microbiological success rate was 81.3%, with no differences between etiologies (Candida spp., bacteria or both). The combination product was well-tolerated, despite the local inflammation before treatment. Discussion and conclusion: Given the etiological diversity of vaginitis, this trial supports the efficacy of a triple-combination product (nystatin, neomycin, polymyxin B) as a first-line local treatment of Candida, bacterial or mixed vaginitis.

Pre-formulation Study for Preparation of Mucoadhesive Buccal Tablets Containing Nystatin and Cashew Gum by Direct Compression

Cashew gum is a branched chain heteropolysaccharide extracted from the cashew tree (Anacardium occidentale L.).Purified cashew gum (PCG) is free of plant contaminants and is highly soluble.Several studies have indicated this polymer can be relevant in the pharmaceutical industry for production of tablets.Recently,our research group reported that PCG can be used as a diluent for tablets produced by direct compression.Nystatin (Nys) is the drug of first choice for treatment of oral candidiasis,in the form of a suspension.The treatment consists of up to six daily doses of a suspension of nys at 500,000 IU,causing low therapeutic adhesion by patients.The objective of this study was to investigate the behavior of PCG together with nys and other excipients (flavoring agents and lubricating agent) for future manufacture of mucoadhesive buccal tablets by direct compression.For that purpose,we performed pre-formulation tests (FTIR,TGA,XRD,solubility,pH,granulometry,swelling degree and powder flow) with physical mixtures of the drug and excipients.The results were excellent,demonstrating that PCG is a polymer with potential for this type of application.

Endostatin specifically targets both tumor blood vessels and lymphatic vessels

Endostatin,a 20 kDa C-terminal fragment of collagen XVIII,was first identified as a potent angiogenic inhibitor.The anti-angiogenic function of endostatin has been well documented during the past decade.Recently,several studies demonstrated that endostatin also inhibits tumor lymphangiogenesis and lymphatic metastasis.However,the exact mechanism that endostatin executes its anti-angiogenic and anti-lymphangiogenic functions remains elusive.In the current mini-review,we briefly summarize recent novel findings,including the functions of endostatin targeting not only angiogenesis but also lymphangiogenesis,and the underlying mechanism by which endostatin internalization regulates its biological functions.