Ketamine and nifedipine protect cultured cortical neurons against injurious effect of glutamate]

The effects of glutamate on cultured cortical neurons and the protective effect of ketamine and nifedipine were studied. On day 10 after plating of the cortical cells from 16-18 day-old fetal rats, the cultures were exposed to 50 mumol.L-1 glutamate and low glucose (1 g.L-1) for 10 min-24 h. The results showed that a release of lactate dehydrogenase (LDH) into the culture supernatant was observed as a function of time. The values of LDH efflux in culture medium was significantly lower than those of controls when the cells were pretreated with ketamine or nifedipine 10 min prior to addition of glutamate. More significant decrease of LDH activity in culture medium was observed when the two drugs were used in combination. These results demonstrate that the dissociated cultured cortical neurons from fetal rat are seriously damaged by glutamate. Such damage could be attenuated by ketamine and nifedipine, suggesting that ketamine and nifedipine may protect neurons from the glutamate toxicity, and the effect of combining ketamine and nifedipine was greater than either ketamine or nifedipine alone.     

Straightforward solid-phase extraction method for the determination of verapamil and its metabolite in plasma in a 96-well extraction plate

Straightforward solid-phase extraction (SPE) methods were developed for the determination of verapamil and its metabolite in a plasma matrix. The spiked plasma sample was pretreated with 2% phosphoric acid followed by two different SPE methods using a Waters Oasis HLB 96-well extraction plate. Recoveries greater than 90% were obtained using both a generic and a selective SPE methods. The generic method is a good starting protocol, and it is applicable to a wide range of compounds. This generic method consists of using 5% methanol as the wash solvent, and 100% methanol for the elution. The limitation of the non-specific method is that it does not remove all plasma constituents that interfere with the quantitation of the metabolite, norverapamil. A second, more specific method was developed using the same Oasis HLB sorbent which removes more plasma interferences and provides cleaner extracts for the HPLC-UV analysis. This selective method uses both the methanol concentration and the pH advantageously to preferentially isolate the analytes of interest from a complex sample matrix. Recoveries of greater than 90% with R.S.D.s less than 3.8% were obtained with this selective method.     

High-affinity aptamers selectively inhibit human nonpancreatic secretory phospholipase A2 (hnps-PLA2)

Evidence is growing that reactive oxygen species (ROS), by-products of (normal) cellular aerobic metabolism, are involved in the pathogenesis of neurodegenerative diseases. One of these diseases is amyotrophic lateral sclerosis (ALS), in which motoneurons die, leading to paralysis and death. It remains uncertain whether ROS are the cause of (apoptotic) motoneuron death in ALS. To further understand the role of ROS in motoneuron death, we investigated the effects of ROS on isolated spinal rat motoneurons in culture. ROS were generated with a combination of iron(III) and ascorbate, or with hydrogen peroxide. Both toxic treatments resulted in a dose-dependent motoneuron death. Iron(III)/ascorbate toxicity was completely prevented with the hydrogen peroxide detoxifying enzyme catalase and partially prevented with the antioxidant vitamin E. SOD1, the enzyme that removes superoxide, did not protect against iron(III)/ascorbate toxicity. ROS treatment caused apoptotic motoneuron death: low doses of iron(III)/ ascorbate or hydrogen peroxide resulted in complete apoptosis ending in nuclear fragmentation, while high doses of ROS resulted in incomplete apoptosis (nuclear condensation). Thus, depending on the dose of ROS, the motoneurons complete the apoptotic pathway (low dose) or are stopped somewhere during this route (high dose).     

Multidimensional chromatography coupled with mass spectrometry for target-based screening

The synthesis of structural analogs and the process of drug discovery have evolved dramatically through recent advances in solid-phase synthesis reagents and automated screening systems. As molecular diversity strategies emerge, the need for automated target-based selection of lead candidates becomes equally important. Multidimensional automated chromatographic techniques coupled to electrospray ionization mass spectrometry facilitate the selection process and provide maximum characterization information in a single screening run. The capture of tightly bound affinity leads by target biomolecules, followed by subsequent release and high-resolution separation with sensitive detection, significantly reduces the time required to identify and characterize lead compounds. This automated multidimensional chromatographic approach coupled with mass spectrometry, Selectronics, was used with several organic and natural libraries to demonstrate an automated target-based screening technique to select for high-affinity binders as potential lead compounds.     

Electroanalytical characteristics of ofloxacin in micellar solution

In a pH 6.30 buffer solution containing 0.001% Tween-80, ofloxacin (OFX) gives a sensitive polarographic wave at -1.46 V (vs SCE), which can be used for the determination of OFX down to 10(-8) mol.L-1. The linear range is from 1.39 x 10(-7) to 1.39 x 10(-5) mol.L-1. The proposed method was applied to determination of OFX in urine and serum samples with relative standard deviation less than 7.0%.     

Phosphoryl transfer reaction regulated by amino acid side chains: a model for phosphoproteins

STUDY OBJECTIVE: To compare the safety and effectiveness of 0.25 mg divided doses of mivacurium chloride to succinylcholine for a 90-second tracheal intubation. DESIGN: Randomized, double-blind, multicenter study in two groups. SETTING: Operating rooms at four university medical centers. PATIENTS: 200 healthy ASA status I and II adult patients scheduled for elective surgery with general anesthesia and endotracheal intubation. INTERVENTIONS: Patients were premedicated with 1 to 2 mg midazolam and 2 micrograms/kg fentanyl. Anesthesia was induced with 2 mg/kg propofol. Group A received 0.25 mg/kg mivacurium given as a divided dose (0.15 mg/kg followed in 30 seconds with 0.1 mg/kg). Group B (control) received 1.5 mg/kg succinylcholine (SCh) preceded two minutes earlier by 50 micrograms/kg d-tubocurarine (dtc). MEASUREMENTS AND MAIN RESULTS: Tracheal intubation grading, train-of-four response of the adductor pollicis, heart rate (HR), and mean arterial blood pressure (MAP) were measured and evaluated. Chi-square analysis was performed for comparison between Group A and Group B with respect to the frequency distribution of intubation using the scores excellent, good, and poor and not possible (combined). Group B had a significantly higher excellent score of intubation than Group A, 84% versus 56% (p < 0.0001). No significant difference was found between the two groups when the scores excellent and good were combined (Fisher's Exact test, p = 0.28). The changes in MAP and HR were similar for the two groups. CONCLUSIONS: When Sch is not desirable, mivacurium 0.25 mg/kg given as a divided dose provides good to excellent intubation conditions 90 seconds after the initial dose without significant changes in MAP or HR. It can be an appropriate alternative for short surgical procedures. It must be emphasized that this conclusion does not apply to rapid-sequence induction-intubation.     

Performance optimizing on multi-function MMIC design

Integration of GaAs BiFET (bipolar-FET) devices to obtain the optimum performance for multiple functions of MMIC design has been achieved. In this study, heterojunction bipolar transistors (HBTs), enhancement mode pseudomorphic HEMTs (E-pHEMTs), and depletion mode pHEMTs are developed for potential applications, including the integration of HBT power amplifier circuitry with pHEMT-based bias control, logic, RF switch, and low-noise amplifier circuitries. Critical processes including gate photolithography and gate recess control are presented and discussed in detail. The enhancement-depletion modes of pHEMT, HBT electrical performance, and uniformity are investigated comprehensively. In addition, power amplifiers and high power switches based on BiFET technology are investigated.     

Adaptive DS-CDMA Receiver with Code Tracking in Phase Unknown Environments

In this paper, we propose and analyze a new noncoherent receiver with PN code tracking for direct sequence code division multiple access (DS-CDMA) communication systems in multipath channels. We employ the decision-feedback differential detection method to detect MDPSK signals. An ";error signal"; is used to update the tap weights and the estimated code delay. Increasing the number of feedback symbols can improve the performance of the proposed noncoherent receiver. For an infinite number of feedback symbols, the optimum weight can be derived analytically, and the performance of the proposed noncoherent receiver approaches to that of the conventional coherent receiver. Simulations show good agreement with the theoretical derivation.