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Continued water quality impairment has introduced serious environmental concerns for health, stream life, agriculture, and industry. In general, water pollution is a resultant of agricultural and industrial activities. We handpicked 150 samples of drinkable water from various parts of the Faisalabad City. The findings revealed that locations fed by industrial waste matter had higher nitrate level, whereas places with superior drainage had lower nitrate content. Almost all the factors in general produced major effects on the leaching of fertilizer (NO3-N) into the soil outline. The current research found that nitrogenous fertilizer in the form of NO3-N was leached up to 150 cm into the soil. In Pakistan, the water table was within 150 cm of the ground surface on 30 percent of the 41 million acres examined. The municipal and industrial wastes of Faisalabad cannot be separated, as industries are situated in residential areas. The mixture is discharged into open land or into drains. None of the samples contained Zn in the tolerance limit (TL refers to the concentration higher than maximum permissible limit). MPL decrease with an increase in distance of the source from the sullage carrier. Fe, Cu and Mn, the results indicate that the sullage carrier has contaminated the ground water up to 300 meters and no water sample was found within TL within 300 meters distance. The results indicate that Fe, Cu, and Mn concentration in ground water has reached to problematic level along unlined section of the sullage carrier. Thus, in this zone a severe Fe, Cu and Mn toxicity has been identified. Pb however, the situation was somewhat different because none of the samples was found within TL after 50 meters distance of source from such sullage carrier. The result of Fe indicates problem in some water samples collected along lined section of sullage carrier. The same situation prevailed for Cu and Mn. Both the metals have contaminated the ground water up to 150 meters. The results of Pb were similar as in case of unlined section of the sullage carrier but it has some problem up to 25 meters. This paper describes some aspects of surface and subsurface water pollution, in addition to best management practices and remedial measures required for minimization environmental hazards.

Derivatives of chlorogenic acid or its analogues were synthesized by coupling protected chlorogenic acid or its analogues with p-octyloxyaniline and selected amino acids. Most of the compounds exhibited significant potency against Cryptococcus neoformans and Candida species with low toxicity to brine shrimps. The 4,5-dihydroxyl groups in the quinic acid moiety were necessary for the activity and introduction of a free amino group increased the inhibitory activity against Aspergillus fumigatus.

The pharmacokinetics and distribution in tissue of several novel triazole antifungal agents were studied in different animal species in order to select an appropriate lead compound. The purpose of the study was also to determine species differences in pharmacokinetics for SYN azoles to select the most appropriate species for secondary efficacy and toxicological evaluation of the selected compound. SYN-2836, SYN-2869, SYN-2903, and SYN-2921 were rapidly absorbed into the systemic circulation and reached maximum concentrations ( C max s) of 7.31 ± 2.53, 6.29 ± 0.85, 6.16 ± 0.39, and 3.41 ± 0.34 μg/ml, respectively, in BALB/c mice after administration of an oral dose of 50 mg/kg of body weight, with bioavailability being greater than 45% in all mice. The areas under the concentration-time curve from time zero to infinity (AUC 0–∞ s) after administration of a single intravenous dose of 20 mg/kg to mice varied between 25.0 and 63.6 μg · h/ml. The half-life was in the range of 4.5 to 6 h. In Sprague-Dawley rats there was no significant difference in AUC 0–∞ after administration of a single intravenous dose of 20 mg/kg, but on oral administration, the bioavailability of SYN-2836 was extremely low, while that of SYN-2869 was only 14.7%. In New Zealand White rabbits the C max and the time to reach C max for SYN-2836 and SYN-2869 after administration of a single oral dose of 50 mg/kg were similar. There were significant differences in AUC 0–∞ and half-life between SYN-2836 and SYN-2869. On the other hand, in beagle dogs the C max and AUC 0–∞ of SYN-2836 after administration of a single oral dose of 30 mg/kg were 4.82 ± 1.54 μg/ml and 41.8 ± 15.7 μg · h/ml, respectively, which were threefold higher than those of SYN-2869. The concentrations of the SYN compounds in tissue indicated that the AUC 0–∞ s of SYN-2836, SYN-2869, SYN-2903, and SYN-2921 in mouse lungs were significantly different from each other. The ratios of the concentrations of the SYN azoles in lungs to those in plasma were also significantly different from those for itraconazole. Among the SYN azoles the highest concentration in the lungs was found for SYN-2869. The higher level of distribution of SYN-2869 into lung tissue was considered to contribute to the potent efficacy in respiratory tract infection models compared with the potency of itraconazole. Significant differences in the pharmacokinetics of these compounds were observed in different animal species, and selection of an animal model for further evaluation was based on results obtained from these studies.

A method for high-throughput Caco-2 permeability screening of drug candidates has been developed using thirteen generic drugs as test compounds. The high throughput was achieved by either a sample pooling or a cassette dosing approach, along with the use of a rapid, simple and sensitive direct injection/on-line guard cartridge extraction/tandem mass spectrometric assay that was also developed in this study. It was of concern that possible drug-drug interactions (e.g., inhibition of P-glycoprotein-mediated transport of a drug by another, and/or competition of the drugs for transport pathways), when the cassette dosing regimen was implemented, may give rise to inconsistent results compared with those attained by a traditional single-drug dosing approach. However, the apparent permeability coefficients of the test drugs across Caco-2 monolayers measured by the sample pooling or cassette dosing (up to five drugs co-administered in this study) strategy were in good conformity with the data obtained by single-drug dosing followed by discrete sample analysis. Copyright © 2000 John Wiley & Sons, Ltd.

A simple and rugged reversed-phase high-performance liquid chromatographic method with ultraviolet absorbance detection at 263 nm was developed and validated for the analysis of novel triazole antifungal agents SYN-2869 and its derivatives in tissues. The method involved homogenization with 0.01 M phosphate buffer (pH 7.8) for lung, brain and spleen tissues. The liver and kidneys were homogenized with acetonitrile:acetone (1:1). The plasma proteins were precipitated with ice-cold acetonitrile and supernatent was evaporated to dryness. The reconstituted samples were injected onto an HPLC system. SYN-2869 was separated from the matrix components on a symmetry C(18) column using a aqueous mobile phase of acetonitrile and water with a flow rate of 1 mL/min. A step gradient of 40-80% acetonitrile eluted SYN-2869 and the internal standard (SYN-2506). The linear range was 0.5-10 microgram/g (r(2) > 0.99). The limit of quantitation was 0.5 microgram/g. The inter-day precision and accuracy for SYN 2869 standard concentration were from 2.6 to 7.4% and from -1.56 to +3.29%, respectively. The method was applied to tissue samples collected from single intravenous administration to mice to evaluate the distribution of these novel antifungal agents to different tissues.

This paper presents liquid chromatography/mass spectrometry (LC/MS) and liquid chromatography/tandem mass spectrometry (LC/MS/MS) approaches for the rapid characterization of three urinary isomeric metabolites and their two precursor metabolites of SYN-2836, a novel antifungal agent, in dogs administered multiple oral doses of the agent (30 mg kg(-1) day(-1)). A collection of correlative data regarding the SYN-2836 metabolites was obtained by LC/MS and LC/MS/MS performed under complementary conditions such as the columns (C(18) vs cyano type), the mobile phase systems (acetonitrile-water-formic acid vs acetonitrile-water-ammonium acetate) and the electrospray ionization modes (positive vs negative). Metabolite identification was accomplished based on not only the LC/MS/MS data (product ion spectra) but also the LC/MS data indicating chromatographic behaviors of the metabolites. SYN-2836 and SYN-2869, an analog of the former, showed almost the same metabolic pathways following the same multiple-dose administration of the individual agents to the dogs. Therefore, correlation analysis in product ion spectra between corresponding metabolites of SYN-2836 and SYN-2869, and also in metabolic pathways between the two agents, was strategically used to facilitate the identification of the SYN-2836 (and SYN-2869 if necessary) metabolites. For the reason that various elucidation strategies were used complementarily, the chemical structures of the metabolites were unambiguously attained and the isomeric metabolites were explicitly differentiated without the use of other analytical methods. The methodologies used in this study may be applicable to metabolite screening of several structurally related agents simultaneously, promoting lead finding and optimization of drug candidates using a metabolism-based approach.

A rapid and rugged solid-phase extraction-liquid chromatographic-electrospray tandem mass spectrometric method has been developed to quantitate two novel human leukocyte elastase inhibitors, SYN-1390 and SYN-1396, in rat plasma. A reversed-phase column and an isocratic mobile phase consisting of acetonitrile-water-formic acid (70:30:0.2, v/v/v) were used. The mass spectrometer was operated in the multiple reaction monitoring mode. For both analytes, standard curves were linear over a working range of 0.1–20 μg ml −1 ( r ≥0.995) and the limit of quantitation was 0.1 μg ml −1 with a 150 μl plasma volume. This assay proved to be useful for the determination of SYN-1390 and SYN-1396 in plasma samples from pharmacokinetic study.

The presence of a neurotoxic amino acid, 3-N-oxalyl-L-2,3-diaminopropanoic acid (β-ODAP), in the seeds of grass pea (Lathyrus sativus) is the cause of an irreversible spastic paraparesis, neurolathyrism, after over-consumption. This is a negative factor in an otherwise very tasty, nutritious, easily cultivated and hardy food crop in Asia and Africa. The reduction of β-ODAP to less than 10% of the original content has been reached by fermenting L sativas Jamalpur seeds with Aspergillus oryzae NRRL 1988 for 48 h, followed by fermentation with Rhizopus oligosporus sp T-3 for 48 h. Other nutritional qualities were also improved in the fermented seed meal: increased content of protein, higher amino acid scores for sulphur-containing and aromatic amino acids, better resistance to high temperature and to oxidation, and drastic reduction of the flatulence factors.

Taking advantage of two scan modes of an electron beam CT scanner (Imatron), we have developed a method utilizing x-ray CT for relating pulmonary perfusion to global and regional anatomy. A high temporal resolution mode, used to follow bolus contrast agent, is combined with a high spatial resolution mode to obtain the structure-function fusion. A software module has been developed for our image analysis package (VIDA) ® to automatically calculate physiologic parameters of flow and integrate these color coded functional measurements into a corresponding high spatial resolution data set. We present the scanning methodology details and give examples from our physiologic based research to demonstrate strengths of combining dynamic and high resolution CT to uniquely characterize pulmonary normal and pathophysiology.

A simple procedure for the precolumn derivatization of toxic and non-toxic non-protein amino acids occurring in the legume crop Lathyrus sativus and other Lathyrus species with phenyl isothiocyanate and an HPLC method for the separation of the derivatives in the nano- and picomole range are reported. The results are compared with those of conventional ion-exchange chromatography for the separation of non-protein amino acids with postcolumn ninhydrin reaction. The relative standard deviations for the two methods are compared.

The γ-glutamyl derivative of β-(isoxazolin-5-on-2-yl)-alanine was found in seedlings of Lens culinaris and Lathyrus sativus. The chemical and spectroscopic properties are compared with its decarboxylation product previously found in seedlings of Lathyrus odoratus. NMR studies of the two derivatives indicate the absence of cyclization and the probability of cis-trans isomers. Some biochemical implications related to potential ways to detoxify Lathyrus sativus are discussed.

To determine regional pulmonary microvascular mean transit times (MTTs), we used electrocardiogram-gated X-ray computed tomographic imaging to follow bolus radiopaque contrast material through the lungs in anesthetized animals (7 dogs and 1 pig, prone and supine). By deconvolution/reconvolution of regional time-attenuation curves obtained from parenchyma and large lobar arteries, we estimated the microvascular residue function and reconstituted the regional microvascular time-attenuation curves and, thus, regional microvascular MTTs. The mean microvascular MTTs in the supine and prone postures were 3.94 ± 1.0 and 3.40 ± 0.84 (mean ± SD), respectively. The dependent-nondependent vertical gradient of MTT was greater in the supine [slope = 0.25 ± 0.10 (SD), P < 0.001 by t-test] than in the prone (−0.03 ± 0.06 in 6 of 8 animals; 2 outliers had positive slopes) posture. In both postures, there was a trend toward faster transit times in the dorsal-basal lung region in six of the eight animals, suggesting gravity-independent higher vascular conductance dorsocaudally. We conclude that deconvolution methods, in association with electrocardiogram-gated high-speed X-ray computed tomography, can provide insights into regional heterogeneity of pulmonary microvascular MTT in vivo.

The biosynthesis of the Lathyrus neurotoxin 3-N-oxalyl- l -2,3-diaminopropanoic acid (β-ODAP) was examined in the ripening seeds and fruit of Lathyrus sativus. It was found that the incorporation of [14C]-label from the precursor β-(isoxazolin-5-on-2-yl)-alanine into β-ODAP occurs in intact fruits as well as in separated pericarp and immature seeds, in both a high and low toxin variety. This incorporation gradually decreases in the pericarp while increasing in the maturing seed. Only in the final stage of maturity is the biosynthesis lower in the low toxin variety. In germinating seeds of Crotalaria incana this incorporation does not take place.

Rationale and Objectives To evaluate the adequacy of multibreath and single-breath stable xenon gas techniques to measure regional ventilation during cardiac-gated, high-speed, multisection imaging, the authors carried out a series of studies using electron-beam computed tomography (CT) and a recently introduced subsecond multisection spiral CT scanner. Materials and Methods In four anesthetized pigs, the authors implemented single-breath and/or dynamic multibreath wash-in and washout protocols with respiratory- and cardiac-gated image acquisition. The effects of varying tidal volume and inspiratory flow rate were evaluated independently. Scanning was done at end expiration to avoid artifacts from partial volumed conducting airways, which are filled with inspired gas concentration during inspiration. Results A single breath of 100% xenon provides adequate enhancement in the lung parenchyma (mean, 32 HU ± 1.85 [standard error]) and should not cause unwanted side effects (mean xenon concentration in lung periphery, 21%). The single-breath method is suitable for studies requiring only short periods of apnea. Using the multibreath method, in dependent portions of the lung, there was close agreement between measured changes and predictions based on the xenon calibration data. More than 10 breaths were needed to clear tracer from poorly ventilated areas, and some nondependent regions demonstrated apparently “linear” rather than exponential clearance curves, possibly reflecting longer washout times. Analysis of wash-in and washout curves revealed vertical ventilation gradients and, at higher inspiratory flow rates, redistribution of ventilation to areas of the lung with greater pathway conductance. Conclusion With careful attention to lung volume and use of cardiac gating, it is now possible to correlate lung structure with function to a degree heretofore not possible.

The in vitro and in vivo activities of four azole compounds belonging to a new series of 2(2,4-difluorophenyl)-3-(4-substituted piperazin-1-yl)-1-(1,2,4-triazol-1-yl) butanol antifungal agents is described. The compounds were selected from a library of azole compounds synthesized by our group. The in vitro activities of Syn2869, Syn2836, Syn2903, and Syn2921 against a panel of over 240 recently collected clinical isolates of yeast and molds were determined, and the results were compared with those obtained with fluconazole (FLC), itraconazole (ITC), and amphotericin B (AMB). The MICs at which 90% of the isolates were inhibited (MIC 90 s) for the four test compounds for strains of Candida spp. ranged from Candida albicans and other Candida sp. strains. Moreover, MIC 90 s for strains of Cryptococcus neoformans , Aspergillus spp., Trichophyton spp., and Microsporum spp. were also low and ranged from C. albicans in a murine systemic infection model and significantly improved the survival rates of the infected mice. The results for Syn2903 were similar to those for FLC, while the other compounds were slightly less effective but had ranges of activities similar to the range of activity of ITC. The compounds were also evaluated against an Aspergillus fumigatus systemic infection. Syn2903 was also superior to ITC, whereas the efficacy data for the other compounds were similar to those for ITC. It was concluded from the data generated for this new series of azole compounds in the studies described above that further pharmacokinetic and toxicologic evaluations are warranted prior to selection of a candidate compound for preclinical testing.

This report presents the structural elucidation of 12 urinary metabolites of SYN-2836, a new antifungal agent showing extensive metabolism in beagle dogs, using complementary liquid chromatography/tandem mass spectrometry (LC/MS/MS) methodologies. The 12 SYN-2836 metabolites were readily divided into four groups by considering that all three members of each group, although differing in masses, exhibited highly similar product ion mass spectra. This suggests that the metabolites within each group share a common major substructure. Therefore, all the grouped SYN-2836 metabolites were strategically identified by characterization of the major substructures followed by determination of the additional small substructures. This grouping strategy greatly facilitated the structural elucidation of these metabolites. Other strategies were also employed to achieve as rapid and unambiguous characterization of the SYN-2836 metabolites as possible. Copyright © 2001 John Wiley & Sons, Ltd.

A simple reversed-phase high-performance liquid chromatography (HPLC) method with UV detection was developed and validated for the quantitation of SYN-2869, a novel triazole antifungal agent and its analogs in rat plasma. The method involved a simple precipitation of plasma protein with acetonitrile (1:10 ratio). The reconstituted sample after evaporation to dryness was injected onto a HPLC column. SYN-2869 and its analogs were separated from the matrix components on a symmetry C18 column using an aqueous mobile phase of acetonitrile and water with a flow rate of 1 ml min(-1). A step gradient of 40-80% acetonitrile eluted all four compounds. The run time was 30 min. The linear range was 0.5 10 microg ml(-1)(r2 > 0.999). The limit of quantitation was 0.5 microg ml(-1). The inter-day precision and accuracy for SYN-2869 standard concentration were from 1.9 to 8.5% and from 1.4 to +/- 4.40%, respectively. The precision and accuracy of intra-day quality control samples were from 4.6 to 5.2% and from 4.6 to 12%, respectively.

A rapid, selective, sensitive and reproducible HPLC-electrospray tandem mass spectrometric method has been developed for the analysis of novel triazole antifungal agents, SYN-2869 and its derivatives (SYN-2836, SYN-2903 and SYN-2921), in rat plasma using SYN-2506 as an internal standard. Isolation of these compounds from plasma and sample desalting were performed by a simple extraction procedure involving protein precipitation, vacuum-drying and reconstitution with acetonitrile. For all the agents, linearity was observed over the range of 10-10,000 ng/ml (ror = 0.996) and the limit of quantitation was 10 ng/ml using a 100-microliter plasma volume. A measurement rate of 400-500 samples/day/instrument could be achieved using this method.

Microvascular red blood cell mean transit time is a crucial parameter underlying basic pulmonary physiology. Dynamic x-ray CT imaging during bolus radiopaque tracer injection offers the ability to make functional measurements throughout the lungs, but is not able to resolve individual microvascular beds. We have implemented a model-free Fast Fourier Transform deconvolution algorithm to extract the microvascular transport characteristics from the acquired time-intensity data. The deconvolved feeding arterial bolus input curves and corresponding regional pulmonary parenchymal 'response' functions provide measures of regional pulmonary tracer residence times, allowing calculation of microvascular transit times for different spatial regions of the pulmonary system. The acquired feeding (main) pulmonary artery and regional pulmonary parenchyma time-intensity curves were fit to gamma variate functions which were then sampled with a temporal resolution of 0.1 seconds. Deconvolution of the feeding arterial and regional parenchymal curves consistently results in bimodal regional residue functions. The two modes consist of a relatively large, sharp, narrow peak approximating a delta function followed by a smaller more dispersed curve. The sharp, narrow peak appears to be due to small artery inclusion in the sampled parenchymal region (partial volume effects). The magnitude of the dominant arterial peak decreases as sampling locations are moved from the less expanded dependent to the more expanded non-dependent lung regions of supine dogs. Mathematical separation of the two modes allowed isolation of the arterial and microvascular components. The shape and transit times of the putative microvascular components agree well with results from similar measurements via microfocal angiography and in vivo microscopy. Reconvolving the microvascular component with the input curve results in a corrected parenchymal curve representing the regional microvascular transport characteristics, free of arterial flow signal contamination. The corrected residue curves can then be used for non-invasive in vivo quantitation of regional organ microvascular transit times, volumes and flows in relation to the existing in vivo anatomy.© (1998) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

We are using the unique features of electron beam CT (EBCT) in conjunction with respiratory and cardiac gating to explore the use of non-radioactive xenon gas as a pulmonary ventilation contrast agent. The goal is to construct accurate and quantitative high-resolution maps of local pulmonary ventilation in humans. We are evaluating xenon-enhanced computed tomography in the pig model with dynamic tracer washout/dilution and single breath inhalation imaging protocols. Scanning is done via an EBCT scanner which offers 50 msec scan aperture speeds. CT attenuation coefficients (image gray scale value) show a linear increase with xenon concentration (r equals 0.99). We measure a 1.55 Hounsfield Unit (HU) enhancement (kV equals 130, mA equals 623) per percentage increase in xenon gas concentration giving an approximately 155 HU enhancement with 100% xenon gas concentration as measured in a plexiglass super-syringe. Early results indicate that a single breath (from functional residual capacity to total lung capacity) of 100% xenon gas provides an average 32 +/- 1.85 (SE) HU enhancement in the lung parenchyma (maximum 50 HU) and should not encounter unwanted xenon side effects. However, changes in lung density occurring during even short breath holds (as short as 10 seconds) may limit using a single breath technique to synchronous volumetric scanning, currently possible only with EBCT. Preliminary results indicate close agreement between measured regional xenon concentration-time curves and theoretical predictions for the same sample. More than 10 breaths with inspirations to as high as 25 cmH2O airway pressure were needed to clear tracer from all lung regions and some regions had nearly linear rather than mono-exponential clearance curves. When regional parenchymal xenon concentration-time curves were analyzed, vertical gradients in ventilation and redistribution of ventilation at higher inspiratory flow rates were consistent with known pulmonary physiology. We present here a works in progress, showing results from two pigs illustrating the high resolution and detailed regional information obtainable with careful attention to cardiac and respiratory gating during a multi-breath washout period.© (1996) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

We present here our initial findings regarding the utility of functional x-ray CT imaging in determining the presence of pulmonary emboli. Recently, x-ray CT has been reported to be a promising technique in detecting pulmonary emboli through direct visualization of the clot as a filling defect of the reconstructed vascular lumen with CT scanning occurring during i.v. contrast drip. To determine whether functional imaging via the dynamic mode of electron beam CT might add to the sensitivity and specificity of pulmonary emboli diagnosis through the visualization of pulmonary parenchymal blood flow and its associated temporal parameters, we scanned 32 pigs and report here our findings on 17 pigs evaluated to date. Findings to date show that the evaluation of flow deficits detected via electron beam CT with a small 2-3 sec. bolus contrast injection has the potential to provide improvement in embolus detection over visual inspection of this section CT/continuous infusion contrast where the viewer is looking for unenhanced regions in the pulmonary arteries.

To help characterize the determinants of the spatial distribution of regional pulmonary structure and function and to characterize a spatial autocorrelatici (SAC) approach, we have applied SAC statistics to our pulmoiiary cine x-ray (1 data ofregional pulmonary blood flow and to various computer derived models (cubes and pyramids, 3-D wedges, and lung shapes inwhich pure "flow" gradients in either the x, y, or z directions were applied). To generate graphs of correlation vs. distance, we binthe data according to distance into a user specified number of groupings and then autocorrelate the data within each bin. Onlyitgions ofpulmonary parenchyma within the same lobe were used. We present the results of our analysis which show that severalregional parameters exhibit a similar negative sloping correlation vs. distance relationship. Results from our computer modelsshow: 1) there is an order dependence of the spatial correlation algorithm when each region pair is used only once, 2) that thenegative correlation vs. distance ielationship can come about solely through the effects of gravity, and 3) that the effect of anobject's shape cii the spatial autocorrelation relationship is minimal. Regional air content follows a spatial distribution patternconsistent with purely gravitational effects.The similarity of the SAC values for other pulmonary functional values such aspuhnonary blood flow, mean transit time, pulmonary blood volume, etc. may relate to their partial dependence on regional alveolarexpausioii. This may be a likely driving force behind the similar spatial distiibutiou of several other parameters. SAC statisticsprovide a unique tool for demonstrating the existence of underlying patterns to distribution of pulmonary function. However,because several regional distribution inhomogeneities can cause the same negative sloping relationship with a zero cross, it is notfully clear how well SAC uniquely defines the driving force describing the spatial distribution of a function. Care needs to be takenin finding appropriate normalization parameters in comparing data as the normalization factor itself can lend structure to spatialautocorrelation. Finally, shape of the spatial autocorrelation function may be as important or more important than slope in definingunderlying structure.

Zinc deficiency and oversupply of iron to the roots of grass pea ( Lathyrus sativus ) induce increases in the content of the neurotoxin β- l -ODAP (3-oxalyl- l -2,3-diaminopropanoic acid) in the ripe seeds. The transport of zinc to the shoots is enhanced by the addition of β- l -ODAP. The neurotoxin of L. sativus is proposed to function as a carrier molecule for zinc ions. Soils, depleted in micronutrients from flooding by monsoon rains (Indian subcontinent) or otherwise poor in available zinc and with high iron content (Ethiopian vertisols), may be responsible for higher incidence of human lathyrism, one of the oldest neurotoxic diseases known to man. A role for brain zinc deficiency in the susceptibility for lathyrism is postulated.

We have developed a method utilizing x-ray CT for relating pulmonary perfusion to global and regional anatomy, allowing for detailed study of structure to function relationships. A thick slice, high temporal resolution mode is used to follow a bolus contrast agent for blood flow evaluation and is fused with a high spatial resolution, thin slice mode to obtain structure- function detail. To aid analysis of blood flow, we have developed a software module, for our image analysis package (VIDA), to produce the combined structure-function image. Color coded images representing blood flow, mean transit time, regional tissue content, regional blood volume, regional air content, etc. are generated and imbedded in the high resolution volume image. A text file containing these values along with a voxel's 3-D coordinates is also generated. User input can be minimized to identifying the location of the pulmonary artery from which the input function to a blood flow model is derived. Any flow model utilizing one input and one output function can be easily added to a user selectable list. We present examples from our physiologic based research findings to demonstrate the strengths of combining dynamic CT and HRCT relative to other scanning modalities to uniquely characterize pulmonary normal and pathophysiology.

The major toxin present in the dry seeds and seedlings of Lathyrus sativus is the neurotoxin 3-N-oxalyl-L-2,3-diaminopropanoic acid (beta-ODAP). The presence of one additional neurotoxin and an osteotoxin in the seedlings increases the overall toxicity. Isolation, purification, and detection of these toxins are described.