Lack of effects of lesions of the dorsal noradrenergic bundle on behavioral vigilance

The effects of 6-hydroxydopamine (6-OHDA)-induced lesions of the dorsal noradrenergic bundle (DNB) were assessed in animals trained in a task designed to measure sustained attention, or vigilance. Infusions of 6-OHDA reduced frontal cortical noradrenaline contents but did not significantly affect striatal and hypothalamic noradrenaline contents. The performance of lesioned animals did not differ significantly from sham-lesioned controls. The performance of both the lesioned and sham-lesioned animals was impaired by the presentation of a visual distractor and by a decrease in the probability for a signal. The results from this study largely coincide with the results from previous studies on the effects of noradrenergic lesions on various aspects of attention. In contrast to the attentional functions assessed in this experiment, the ability to detect and select stimuli that are associated with activation of sympathetic functions is hypothesized to be sensitive to the effects of DNB lesions.     

Bronchoalveolar lavage studies in children without parenchymal lung disease: cellular constituents and protein levels

The hepatotoxicity of acetaminophen overdose depends on the metabolic activation to a toxic reactive metabolite by the hepatic mixed function oxidases. There is evidence that an increase in cytosolic Ca2+ is involved in acetaminophen hepatotoxicity. The effects of the Ca2+-antagonists nifedipine (NF), verapamil (V), diltiazem (DL) and of the calmodulin antagonist trifluoperazine (TFP) on the activity of some drug-metabolizing enzyme systems, lipid peroxidation and acute acetaminophen toxicity were studied in male albino mice. No changes in the drug-metabolizing enzyme activities studied and in the cytochrome P-450 and b5 contents were observed 1 h after oral administration of V (20 mg/kg). DL (70 mg/kg) and TFP (3 mg/kg). NF (50 mg/kg) increased cytochrome P-450 content, NADPH-cytochrome c reductase and ethylmorphine-N-demethylase activities. DL and TFP significantly decreased lipid peroxidation. NF, V, DL and TFP administered 1 h before acetaminophen (700 mg/kg orally) increased the mean survival time of animals. A large increase of serum aspartate aminotransferase(AST), and liver weight and depletion of liver reduced glutathione (GSH) occurred in animals receiving toxic acetaminophen dose. NF, V and DL prevented and TFP decreased the acetaminophen-induced hepatic damage measured both by plasma AST and by liver weight. NF, V, DL and TFP changed neither the hepatic GSH level nor the GSH depletion provoked by the toxic dose of acetaminophen. This suggests that V, DL and TFP do not influence the amount of the acetaminophen toxic metabolite formed in the liver. The possible mechanism of the protective effect of NF, V, DL and TFP on the acetaminophen-induced toxicity is discussed.     

Liquid Aspiration and Dispensing Based on an Expanding PDMS Composite

In this paper, we present the development of active liquid aspiration and dispensing units designed for vertical, as well as lateral, liquid aspiration. The devices are based on a single-use thermally expanding polydimethylsiloxane (PDMS) composite, which allows altering its surface topography by means of individually addressable integrated heaters. Devices are designed in order to create an enclosed cavity in the system, due to locally expanding the initially unstructured composite. This enables negative volume displacement and leads to the event of liquid aspiration. To enable this device functionality, two different techniques of selectively creating permanent PDMS bonds have been developed. One approach utilizes the plasma-assisted PDMS bonding technique, together with a patterned antistiction layer to form reversibly, as well as irreversibly, bonded regions. Another approach utilizes microcontact printing of PDMS curing agent, which serves as a patterned intermediate layer for adhesive bonding. Fabricated prototype devices successfully demonstrated the aspiration and release of liquid volumes ranging from 28 to 815 nL. The devices are entirely fabricated from low-cost materials, using wafer-level processes only and do not require external means for liquid actuation.     

7-nitroindazole attenuates 6-hydroxydopamine-induced spatial learning deficits and dopamine neuron loss in a presymptomatic animal model of Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder in which loss of dopaminergic (DA) neurons (>50%) in the substantia nigra (SN) precedes most of the overt motor symptoms, making early diagnosis and treatment interventions difficult. Because PD has been associated with free radicals generated by nitric oxide, this study tested whether treatments of 7-nitroindazole (7NI), a nitric-oxide-synthase inhibitor, could reduce cognitive deficits that often emerge before overt motor symptoms in a presymptomatic rat model of PD. Rats were given intraperitoneal injections of 50 mg/kg 7NI (or vehicle) just before receiving bilateral, intrastriatal injections of the DA-toxin, 6-hydroxydopamine (6-OHDA). The rats were then given a battery of motor tasks, and their learning ability was assessed using a spatial reversal task in a water-T maze. Results indicate that 7NI treatments attenuate 6-OHDA-induced spatial learning deficits and protect against DA cell loss in the SN, suggesting that 7NI may have potential as an early, presymptomatic pharmacotherapy for PD. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Small‐Scale Thermal Studies of Volatile Homemade Explosives

Several homemade or improvised explosive mixtures that either contained volatile components or produced volatile products were examined using standard small‐scale safety and thermal (SSST) testing that employed differential scanning calorimetry (DSC) techniques (constant heating rate and standard sample holders). KClO₃ and KClO₄ mixtures with dodecane exhibited different enthalpy behavior when using a vented sample holder in contrast to a sealed sample holder. The standard configuration produced profiles that exhibited only endothermic transitions. The sealed system produced profiles that exhibited additional exothermic transitions absent in the standard configuration produced profiles. When H₂O₂/fuel mixtures were examined, the volatilization of the peroxide (endothermic) dominated the profiles. When a sealed sample holder was used, the energetic releases of the mixture could be clearly observed. For AN and AN mixtures, the high temperature decomposition appears as an intense endothermic event. Using a nominally sealed sample holder also did not adequately contain the system. Only when a high‐pressure rated sample holder was used the high temperature decomposition of the AN could be detected as an exothermic release. The testing was conducted during a proficiency (or round‐robin type) test that included three U.S. Department of Energy and two U.S. Department of Defense laboratories. In the course of this proficiency test, certain HMEs exhibited thermal behavior that was not adequately accounted for by standard techniques. Further examination of this atypical behavior highlighted issues that may have not been recognized previously because some of these materials are not routinely tested. More importantly, if not recognized, the SSST testing results could lead to inaccurate safety assessments. This study provides examples, where standard techniques can be applied, and results can be obtained, but these results may be misleading in establishing thermal properties.     

Small‐Scale Safety Testing of Ammonium Nitrate and Mixtures

Ammonium nitrate (AN), gunpowder (GP), and an ammonium nitrate gunpowder mixture (AN/GP) were studied for impact sensitivity by four laboratories using the drop hammer apparatus. Bruceton and Neyer methods were used as experimental protocols and for data reduction. The results are presented as 50 % probability of reaction (DH₅₀). For AN, the DH₅₀ values are widely varied among the participants, from sensitive to completely insensitive (limit of the equipment), with no real correlation among results. GP and the AN/GP mixture exhibited much more sensitivity overall and were in some cases within statistical values extrapolated from previous studies of RDX. The variability in results for the AN data is attributed to the difficulty in determining a positive reaction event for AN, as detailed by Neyer experiments and photography during positive reactions. Variability in results for the GP and AN/GP mixtures is attributed to equipment environment and detection criteria. This work was performed by the Integrated Data Collection Analysis (IDCA) program, a multi‐laboratory effort to standardize safety testing of improvised or homemade explosives funded by the Department of Homeland Security.     

Lipid hydroperoxides induce apoptosis in T cells displaying a HIV-associated glutathione peroxidase deficiency

8E5 is a chronically human immunodeficiency virus (HIV)-infected human T cell line, which we have previously shown to be extremely susceptible to hydrogen peroxide (H2O2)-induced apoptosis due to a HIV-associated catalase deficiency. Here we report that HIV gene expression additionally renders 8E5 cells 10-fold more sensitive than either uninfected A3.01 cells or HIV-infected but nonexpressing 8E5L cells to killing by 15-hydroperoxyeicosatetraenoic acid (15-HPETE), as well as several other hydroperoxy fatty acids. Whereas the viability of A3.01 and 8E5L cells was relatively unaffected by exposure to 10 microM 15-HPETE, similarly treated 8E5 cells underwent apoptosis, as demonstrated by morphological changes and the presence of fragmented DNA. The unique susceptibility of 8E5 cells was attributable to their inability to convert 15-HPETE to 15-hydroxy-eicosatetraenoic acid (15-HETE) owing to a marked reduction in glutathione peroxidase activity. Since oxidized lipids have been reported to accumulate in oxidatively stressed, HIV-infected individuals, a HIV-associated glutathione peroxidase deficiency may contribute to the depletion of CD4 T cells that occurs in the acquired immune deficiency syndrome (AIDS).