Association of MRI T1 relaxation time with neuropsychological test performance in manganese- exposed welders.

This study examines the results of neuropsychological testing of 26 active welders and 17 similar controls and their relationship to welders' shortened MRI T1 relaxation time, indicative of increased brain manganese (Mn) accumulation. Welders were exposed to Mn for an average duration of 12.25 years to average levels of Mn in air of 0.11±0.05mg/m3. Welders scored significantly worse than controls on Fruit Naming and the Parallel Lines test of graphomotor tremor. Welders had shorter MRI T1 relaxation times than controls in the globus pallidus, substantia nigra, caudate nucleus, and the anterior prefrontal lobe. 63% of the variation in MRI T1 relaxation times was accounted for by exposure group. In welders, lower relaxation times in the caudate nucleus and substantia nigra were associated with lower neuropsychological test performance on tests of verbal fluency (Fruit Naming), verbal learning, memory, and perseveration (WHO-UCLA AVLT). Results indicate that verbal function may be one of the first cognitive domains affected by brain Mn deposition in welders as reflected by MRI T1 relaxation times.

Vagus nerve stimulation magnet activation for seizures: a critical review.

Some patients receiving VNS Therapy report benefit from manually activating the generator with a handheld magnet at the time of a seizure. A review of 20 studies comprising 859 subjects identified patients who reported on-demand magnet mode stimulation to be beneficial. Benefit was reported in a weighted average of 45% of patients (range 0-89%) using the magnet, with seizure cessation claimed in a weighted average of 28% (range 15-67%). In addition to seizure termination, patients sometimes reported decreased intensity or duration of seizures or the post-ictal period. One study reported an isolated instance of worsening with magnet stimulation (Arch Pediatr Adolesc Med, 157, 2003 and 560). All of the reviewed studies assessed adjunctive magnet use. No studies were designed to provide Level I evidence of efficacy of magnet-induced stimulation. Retrospective analysis of one pivotal randomized trial of VNS therapy showed significantly more seizures terminated or improved in the active stimulation group vs the control group. Prospective, controlled studies would be required to isolate the effect and benefit of magnet mode stimulation and to document that the magnet-induced stimulation is the proximate cause of seizure reduction. Manual application of the magnet to initiate stimulation is not always practical because many patients are immobilized or unaware of their seizures, asleep or not in reach of the magnet. Algorithms based on changes in heart rate at or near the onset of the seizure provide a methodology for automated responsive stimulation. Because literature indicates additional benefits from on-demand magnet mode stimulation, a potential role exists for automatic activation of stimulation.

Cajachalcone: An Antimalarial Compound from Cajanus cajan Leaf Extract.

Cajanus cajan L, a member of the family Fabaceae, was identified from the Nigerian antimalarial ethnobotany as possessing antimalarial properties. The bioassay-guided fractionation of the crude methanol extract of C. cajan leaves was done in vitro using the multiresistant strain of Plasmodium falciparum (K1) in the parasite lactate dehydrogenase assay. Isolation of compound was achieved by a combination of chromatographic techniques, while the structure of the compound was elucidated by spectroscopy. This led to the identification of a cajachalcone, 2',6'-dihydroxy-4-methoxy chalcone, as the biologically active constituent from the ethyl acetate fraction. Cajachalcone had an IC50 value of 2.0 µ g/mL (7.4 µ M) and could be a lead for anti-malarial drug discovery.

Prenylated flavonoid derivatives from the bark of Erythrina addisoniae.

Two new prenylated flavanones, 2 S-3'-(2-hydroxy-3-methylbut-3-enyl)licoflavone-4'-methyl ether ( 3) and 2 S-3'-(2-hydroxy-3-methylbut-3-enyl)abyssinone II ( 4), and four known flavanones ( 1, 2, 5, 6) were isolated from the stem bark of Erythrina addisoniae. The structures were elucidated on the basis of their spectroscopic and physicochemical data. None of the compounds showed antioxidative properties. 4'-Methylabyssinone V ( 1) and abyssinoflavanone VII ( 6) showed moderate cytotoxic activity (IC 50 = 5 and 3.5 micromol/L, respectively), but apoptosis (caspase-3/7-activation, nuclear fragmentation) was selectively induced by abyssinoflavanone VII ( 6).

Antiplasmodial compounds from Cassia siamea stem bark extract.

Cassia siamea L. (Fabaceae) was identified from the southwest Nigerian ethnobotany as a remedy for febrile illness. This led to the bioassay-guided fractionation of stem bark of the plant extract, using the parasite lactate dehydrogenase assay and multi-resistant strain of Plasmodium falciparum (K1) for assessing the in vitro antimalarial activity. Emodin and lupeol were isolated from the ethyl acetate fraction by a combination of chromatographic techniques. The structures of the compounds were determined by spectroscopy, co-spotting with authentic samples and comparison with literature data. Both compounds were found to be the active principles responsible for the antiplasmodial property with IC(50) values of 5 microg/mL, respectively.

Pterocarpans phaseollin and neorautenol isolated from Erythrina addisoniae induce apoptotic cell death accompanied by inhibition of ERK phosphorylation.

The genus Erythrina (Leguminosae), consisting of over 100 different species, is distributed in tropical regions. In traditional medicine, Erythrina species are used to treat cancer, but little is known about the anticancer mechanisms. From the stem bark of Erythrina addisoniae Hutch. & Dalziel, six prenylated pterocarpans were isolated and analysed for pharmacological activity: While calopocarpin, cristacarpin, orientanol c, and isoneorautenol showed only a weak or moderate toxicity in H4IIE hepatoma cells (EC(50)-value> 25 microM), the toxicity of neorautenol and phaseollin was in the low micromolar range (EC(50)-value: 1 and 1.5 microM, respectively). We further focused on these two substances showing that both increased caspase 3/7 activity and nuclear fragmentation as markers for apoptotic cell death. Neorautenol (10 microM, 2h), but not phaseollin induced the formation of DNA strand breaks (comet assay). Both substances showed no effect on NF-kappaB signalling (SEAP assay: basal activity and stimulation with TNF-alpha), on the other hand both pterocarpans (10 microM, 2 h) decreased the activation of the ERK kinase (p44/p42), an mitogen activated protein kinase which is associated with cell proliferation. We conclude that the pterocarpans phaseollin and neorautenol may be responsible for the anticarcinogenic actions of the plant extract reported in the literature. Further analysis of these substances may lead to new pharmacons to be used in cancer therapy.

Correlation of hyperforin content of Hypericum perforatum (St John's Wort) extracts with their effects on alcohol drinking in C57BL/6J mice: a preliminary study.

Extracts of the herb St John's Wort have been shown to reduce alcohol intake in alcohol-preferring rats, but it is not known which of the constituent(s) are responsible for this effect. In this study, the effect of a crude methanolic extract of Hypericum perforatum (negligible hyperforin content) on alcohol drinking in C57BL/6J alcohol-preferring mice was compared with that of a hyperforin-rich extract (45% hyperforin) prepared by extracting the herb with supercritical carbon dioxide. The dose of the hyperforin-rich extract required to significantly reduce 10% ethanol intake (5 mg/kg) was 125-fold less than that required for the crude extract (625 mg/kg), and was comparable to the dose of fluoxetine (10 mg/kg) required to produce a similar effect. None of these agents significantly affected water intake. These results suggest that the effects of H. perforatum extracts on alcohol drinking behaviour are due to the hyperforin content of the herb rather than to other, more polar constituents. Hyperforin is an unstable compound and this study also highlights the effect of different methods of extract preparation on hyperforin content.

Crystallization and preliminary X-ray analysis of the antimalarial and cytotoxic alkaloid cryptolepine complexed with the DNA fragment d(CCTAGG)2.

Crystals of the indoloquinoline alkaloid cryptolepine complexed with the DNA fragment d(CCTAGG)(2) have been grown by the hanging-drop technique at 293 K using ammonium sulfate as the precipitating agent. Over a period of three weeks, yellow tapering bullet-shaped crystals grew to maximum dimensions of 0.2 x 0.1 x 0.1 mm. The crystals belong to space group P6(4), with unit-cell parameters a = b = 29.960, c = 39.64 A, alpha = beta = 90, gamma = 120 degrees, and diffract to 1.4 A.

Synthesis and evaluation of cryptolepine analogues for their potential as new antimalarial agents.

The indoloquinoline alkaloid cryptolepine 1 has potent in vitro antiplasmodial activity, but it is also a DNA intercalator with cytotoxic properties. We have shown that the antiplasmodial mechanism of 1 is likely to be due, at least in part, to a chloroquine-like action that does not depend on intercalation into DNA. A number of substituted analogues of 1 have been prepared that have potent activities against both chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum and also have in common with chloroquine the inhibition of beta-hematin formation in a cell-free system. Several compounds also displayed activity against Plasmodium berghei in mice, the most potent being 2,7-dibromocryptolepine 8, which suppressed parasitemia by 89% as compared to untreated infected controls at a dose of 12.5 mg kg(-1) day(-1) ip. No correlation was observed between in vitro cytotoxicity and the effect of compounds on the melting point of DNA (DeltaT(m) value) or toxicity in the mouse-malaria model.

Antiplasmodial activities of some Ghanaian plants traditionally used for fever/malaria treatment and of some alkaloids isolated from Pleiocarpa mutica; in vivo antimalarial activity of pleiocarpine.

Fourteen Ghanaian plants used in folk medicine to treat fever/malaria were screened for activity against Plasmodium falciparum (strain K1) and were tested for general toxicity to the brine shrimp. Extracts from three of the plants, Pleiocarpa mutica, Cleistopholis patens and Uvaria chamae were found to have significant antiplasmodial activity. The extract of U. chamae was toxic to brine shrimps. These findings lend support to the use of these plants in traditional medicine. Possible toxicity due to U. chamae is a cause for concern. Five known alkaloids, pleiocarpine (1), kopsinine (2), pleiocarpamine (3), eburnamine (4) and pleiomutinine (5) were isolated from the roots of P. mutica. This is the first report of the occurrence of (4) in P. mutica. Compound (5) was the most active against P. falciparum (IC50 = 5 microM). Although (1) was inactive against malaria parasites in vitro, it was moderately active against P. berghei in mice (25 mg kg(-1) daily for 4 days reduced parasitaemia by 28.5% compared to untreated controls).

Next-Generation NASA Airborne Oceanographic Lidar System.

The complete design and flight test of the next-generation Airborne Oceanographic Lidar (AOL-3) is detailed. The application of new technology has allowed major reductions in weight, volume, and power requirements compared with the earlier AOL sensor. Subsystem designs for the new AOL sensor include new technology in fiber optics, spectrometer detector optical train, miniature photomultiplier modules, dual-laser wavelength excitation from a single small laser source, and new receiver optical configuration. The new design reduced telescope size and maintained the same principal fluorescence and water Raman bands but essentially retained a comparable measurement accuracy. A major advancement is the implementation of single-laser simultaneous excitation of two physically separate oceanic target areas: one stimulated by 532 nm and the other by 355 nm. Backscattered fluorescence and Raman signals from both targets are acquired simultaneously by use of the same telescope and spectrometer-detector system. Two digital oscilloscopes provide temporal- and depth-resolved data from each of seven spectral emission bands.

Airborne polarized lidar detection of scattering layers in the ocean.

A polarized lidar technique based on measurements of waveforms of the two orthogonal-polarized components of the backscattered light pulse is proposed to retrieve vertical profiles of the seawater scattering coefficient. The physical rationale for the polarized technique is that depolarization of backscattered light originating from a linearly polarized laser beam is caused largely by multiple small-angle scattering from particulate matter in seawater. The magnitude of the small-angle scattering is determined by the scattering coefficient. Therefore information on the vertical distribution of the scattering coefficient can be derived potentially from measurements of the time-depth dependence of depolarization in the backscattered laser pulse. The polarized technique was verified by field measurements conducted in the Middle Atlantic Bight of the western North Atlantic Ocean that were supported by in situ measurements of the beam attenuation coefficient. The airborne polarized lidar measured the time-depth dependence of the backscattered laser pulse in two orthogonal-polarized components. Vertical profiles of the scattering coefficient retrieved from the time-depth depolarization of the backscattered laser pulse were compared with measured profiles of the beam attenuation coefficient. The comparison showed that retrieved profiles of the scattering coefficient clearly reproduce the main features of the measured profiles of the beam attenuation coefficient. Underwater scattering layers were detected at depths of 20-25 m in turbid coastal waters. The improvement in dynamic range afforded by the polarized lidar technique offers a strong potential benefit for airborne lidar bathymetric applications.

A review of antimycobacterial natural products.

Tuberculosis is a chronic infectious disease caused by several species of mycobacteria. Due to multi-drug resistant strains of mycobacteria and to a high prevalence of tuberculosis in patients who have acquired human immunodeficiency syndrome (AIDS), the number of patients infected with the disease is increasing worldwide. Thus there is an urgent need for new effective antimycobacterial agents to replace those currently in use. In this instance, the plant kingdom is undoubtedly a valuable source for new anti-tuberculosis agents. The present review article reports the findings from an extensive literature search of all plants that have been assessed for antimycobacterial/antitubercular activity over the past 20-30 years. An attempt has been made to summarize the information in order to highlight those promising plant species which are worthy of further investigation as leads for drug development. Over 350 plant species from a wide range of families and origins, containing various chemical classes of compounds, have been screened for such activity. A review of the relevant in vitro assays using different species of pathogenic and non-pathogenic mycobacteria is also included.

Antiplasmodial and antiamoebic activities of medicinal plants from Sierra Leone.

Crude ethanol extracts of 18 medicinal plants from Sierra Leone, West Africa were examined for antiplasmodial activity against Plasmodium falciparum, using an in vitro microtest. Eleven of these extracts were also screened for in vitro antiamoebic activity against Entamoeba histolytica. Only one plant extract, Triclisia patens (Menispermaceae) showed significant antiplasmodial activity (IC(50) = 8 microg/mL). None of the plant extracts was effective against Entamoeba histolytica.

In vitro antiplasmodial, antiamoebic, and cytotoxic activities of some monomeric isoquinoline alkaloids.

Twenty-one alkaloids have been assessed for activities against Plasmodium falciparum (multidrug- resistant strain K1) in vitro; 18 of these are reported for the first time. Two protoberberine alkaloids, dehydrodiscretine and berberine, were found to have antiplasmodial IC(50) values less than 1 M, while seven alkaloids-allocrytopine, columbamine, dehydroocoteine, jatrorrhizine, norcorydine, thalifendine, and ushinsunine-had values between 1 and 10 M. These results are discussed in the context of structure-activity relationships. Compounds were also assessed for antiamoebic and cytotoxic activities, but none was significantly active except for berberine, which was moderately cytotoxic.

Short-pulse pump-and-probe technique for airborne laser assessment of Photosystem II photochemical characteristics.

The development of a technique for laser measurement of fPhotosystem II (PS II) photochemical characteristics of phytoplankton and terrestrial vegetation from an airborne platform is described. Results of theoretical analysis and experimental study of pump-and-probe measurement of the PS II functional absorption cross-section and photochemical quantum yield are presented. The use of 10 ns probe pulses of PS II sub-saturating intensity provides a significant, up to 150-fold, increase in the fluorescence signal compared to conventional 'weak-probe' protocol. Little effect on the fluorescence yield from the probe-induced closure of PS II reaction centers is expected over the short pulse duration, and thus a relatively intense probe pulse can be used. On the other hand, a correction must be made for the probe-induced carotenoid triplet quenching and singlet-singlet annihilation. A Stern-Volmer model developed for this correction assumes a linear dependence of the quenching rate on the laser pulse fluence, which was experimentally validated. The PS II saturating pump pulse fluence (532 nm excitation) was found to be 10 and 40 mumol quanta m(-2) for phytoplankton samples and leaves of higher plants, respectively. Thirty mus was determined as the optimal delay in the pump-probe pair. Our results indicate that the short-pulse pump-and-probe measurement of PS II photochemical characteristics can be implemented from an airborne platform using existing laser and LIDAR technologies.

Airborne test of laser pump-and-probe technique for assessment of phytoplankton photochemical characteristics.

Initial results of the airborne LIDAR measurement of photochemical quantum yield, Phi(Po), and functional absorption cross-section, sigma(PS II), of Photosystem II (PS II) are reported. NASA's AOL3 LIDAR was modified to implement short-pulse pump-and-probe (SP-P&P) LIDAR measurement protocol. The prototype system is capable of measuring a pump-induced increase in probe-stimulated chlorophyll fluorescence, DeltaF/F(sat), along with the acquisition of ;conventional' LIDAR-fluorosensor products from an operational altitude of 150 m. The use of a PS II sub-saturating probe pulse increases the response signal but also results in excessive energy quenching (EEQ) affecting the DeltaF/F(sat) magnitude. The airborne data indicated up to a 3-fold EEQ-caused decline in DeltaF/F(sat), and 2-fold variability in the EEQ rate constant over a spatial scale a few hundred kilometers. Therefore, continuous monitoring of EEQ parameters must be incorporated in the operational SP-P&P protocol to provide data correction for the EEQ effect. Simultaneous airborne LIDAR measurements of Phi(Po) and sigma(PS II) with EEQ correction were shown to be feasible and optimal laser excitation parameters were determined. Strong daytime DeltaF/F(sat) decline under ambient light was found in the near-surface water layer over large aquatic areas. An example of SP-P&P LIDAR measurement of phytoplankton photochemical and fluorescent characteristics in the Chesapeake Bay mouth is presented. Prospects for future SP-P&P development and related problems are discussed.

Laboratory investigation of human deaths from vampire bat rabies in Peru.

In the spring of 1996, multiple cases of an acute febrile illness resulting in several deaths in remote locations in Peru were reported to the Centers for Disease Control and Prevention (CDC). The clinical syndromes for these cases included dysphagia and encephalitis. Because bat bites were a common occurrence in the affected areas, the initial clinical diagnosis was rabies. However, rabies was discounted primarily because of reported patient recovery. Samples of brain tissue from two of the fatal cases were received at CDC for laboratory confirmation of the rabies diagnosis. An extensive array of tests on the formalin-fixed tissues confirmed the presence of both rabies viral antigen and nucleic acid. The virus was shown to be most closely related to a vampire bat rabies isolate. These results indicate the importance of maintaining rabies in the differential diagnosis of acute febrile encephalitis, particularly in areas where exposure to vampire bats may occur.

Satellite retrieval of inherent optical properties by inversion of an oceanic radiance model: a preliminary algorithm.

A previously published radiance model inversion theory has been field tested by using airborne water-leaving radiances to retrieve the chromophoric dissolved organic matter (CDOM) and detritus absorption coefficient, the phytoplankton absorption coefficient, and the total backscattering coefficient. The radiance model inversion theory was tested for potential satellite use by comparing two of the retrieved inherent optical properties with concurrent airborne laser-derived truth data. It was found that (1) matrix inversion of water-leaving radiances is well conditioned even in the presence of instrument-induced noise, (2) retrieved CDOM and detritus and phytoplankton absorption coefficients are both in reasonable agreement with absorption coefficients derived from airborne laser-induced fluorescence spectral emissions, (3) the total backscattering retrieval magnitude and variability are consistent with expected values for the Middle Atlantic Bight, and (4) the algorithm performs reasonably well in Sargasso Sea, Gulf Stream, slope, and shelf waters but is less consistent in coastal waters.

Satellite retrieval of the absorption coefficient of phytoplankton phycoerythrin pigment: theory and feasibility status.

Oceanic radiance model inversion methods are used to develop a comprehensive algorithm for retrieval of the absorption coefficients of phycourobilin (PUB) pigment, type I phycoerythrobilin (PEB) pigment rich in PUB, and type II PEB deficient in PUB pigment (together with the usual "big three" inherent optical properties: the total backscattering coefficient and the absorption coefficients of chromophoric dissolved organic matter (CDOM)-detritus and phytoplankton). This fully modeled inversion algorithm is then simplified to yield a hybrid modeled-unmodeled inversion algorithm in which the phycoerythrin (PE) absorption coefficient is retrieved as unmodeled 488-nm absorption (which exceeds the modeled phytoplankton and the CDOM-detritus absorption coefficients). Each algorithm was applied to water-leaving radiances, but only hybrid modeled-unmodeled inversions yielded viable retrievals of the PE absorption coefficient. Validation of the PE absorption coefficient retrieval was achieved by relative comparison with airborne laser-induced PEB fluorescence. The modeled-unmodeled retrieval of four inherent optical properties by direct matrix inversion is rapid and well conditioned, but the accuracy is strongly limited by the accuracy of the three principal inherent optical property models across all four spectral bands. Several research areas are identified to enhance the radiance-model-based retrievals: (a) improved PEB and PUB absorption coefficient models, (b) PE spectral shifts induced by PUB chromophore substitution at chromophore binding sites, (c) specific absorption-sensitive phytoplankton absorption modeling, (d) total constituent backscattering modeling, (e) unmodeled carotinoid and phycocyanin absorption that are not now accounted for in the chlorophyll-dominated phytoplankton absorption coefficient model, and (f) iterative inversion techniques to solve for six constituents with only five radiances. Although considerable progress has been made toward the satellite recovery of PE absorption, the maturity of the retrieval is presently insufficient for routine global application. Instead it must currently be used on a regional basis where localized ship and aircraft validation can be made available. The algorithm was developed for the MODIS (Moderate-Resolution Imaging Spectroradiometer) sensor but is applicable to any sensor having comparable band locations.