Identifying populations potentially exposed to agricultural pesticides using remote sensing and a Geographic Information System.

Pesticides used in agriculture may cause adverse health effects among the population living near agricultural areas. However, identifying the populations most likely to be exposed is difficult. We conducted a feasibility study to determine whether satellite imagery could be used to reconstruct historical crop patterns. We used historical Farm Service Agency records as a source of ground reference data to classify a late summer 1984 satellite image into crop species in a three-county area in south central Nebraska. Residences from a population-based epidemiologic study of non-Hodgkin lymphoma were located on the crop maps using a geographic information system (GIS). Corn, soybeans, sorghum, and alfalfa were the major crops grown in the study area. Eighty-five percent of residences could be located, and of these 22% had one of the four major crops within 500 m of the residence, an intermediate distance for the range of drift effects from pesticides applied in agriculture. We determined the proximity of residences to specific crop species and calculated crop-specific probabilities of pesticide use based on available data. This feasibility study demonstrated that remote sensing data and historical records on crop location can be used to create historical crop maps. The crop pesticides that were likely to have been applied can be estimated when information about crop-specific pesticide use is available. Using a GIS, zones of potential exposure to agricultural pesticides and proximity measures can be determined for residences in a study.

In Situ Single-Crystal X-ray Diffraction Study of Crystallization Kinetics in Clathrasil Dodecasil-3C.

The formation of single crystals of the clathrasil dodecasil-3C from a solvothermal synthesis has been followed by in situ diffraction techniques using synchrotron radiation and an image-plate area detector. The high intensity of the X-ray beam, coupled with the ability to record time-resolved two-dimensional data using the image plates, allowed the crystallization kinetics to be studied and rate expressions to be fitted to the crystallization curves.

Neonatal methylmercury poisoning in the rat: effects on development of peripheral sympathetic nervous system. Neuronal participation in methylmercury-induced cardiac and renal overgrowth.

The effects of neonatal CH3-Hg exposure on development and function of peripheral catecholaminergic synapses were examined by measuring tissue norepinephrine (NE) levels and turnover rates and cardiac biochemical responses to sympathetic reflex stimulation. In the rat, cardiac sympathetic neurotransmission normally develops towards the end of the first week postnatally; however, pups given CH3-Hg showed responses to sympathetic reflex stimulation as early as 2 days of age. The accelerated maturation of cardiac sympathetic effect was accompanied by initial enhancement of NE levels and turnover. This effect appeared to be specific to the heart, as kidney displayed subnormal NE levels in CH3-Hg-treated animals. Since neonatal CH3-Hg produces heart and kidney overgrowth, we examined the potential role of sympathetic input in altered tissue growth, utilizing chemical sympathectomy with 6-hydroxydopamine (6-OHDA). Sympathectomy inhibited the early phase of renal overgrowth, suggesting that sympathetic nerves participate in the initial effect of CH3-Hg on this tissue; however, 6-OHDA did not influence later phases of renal enlargement nor did it alter the CH3-Hg-induced cardiac overgrowth. These results indicate that neonatal exposure to CH3-Hg alters the synaptic development of peripheral catecholamine neurons, which may play a role in some of the subsequent effects on tissue development.

Effects of alpha-fluoromethylhistidine (FMH), an irreversible inhibitor of histidine decarboxylase, on development of brain histamine and catecholamine systems in the neonatal rat.

Daily administration of FMH to neonatal rats produced long-lasting inhibition of histidine decarboxylase in hypothalamus and cerebral cortex and led to depletion of histamine in both brain regions. The onset of depletion was more rapid in cerebral cortex, a region in which non-neurotransmitter pools of histamine predominate in early postnatal life, appearing as early as postnatal day 3; depletion in the hypothalamus, a region rich in histaminergic neuronal projections, appeared later. No effects were seen on body or brain growth, nor was development of other biogenic amine systems affected. FMH thus provides a selective probe for examining the role of histamine in brain development.

Role of ornithine decarboxylase and the polyamines in nervous system development: Short-term postnatal administration of α-difluoromethylornithine, an irreversible inhibitor of ornithine decarboxylase.

The role of ornithine decarboxylase (ODC) and the polyamines in development of central and peripheral catecholaminergic neurons was examined through the use of α-difluoromethylornithine (DFMO), a specific irreversible inhibitor of ODC. Short-term postnatal administration of DFMO (500 mg/kg daily on days 1-6) to neonatal rats resulted in effective inhibition of ODC and depletion of both putrescine and spermidine in brain, heart and kidney; after cessation of DFMO administration, polyamine levels returned to normal by 10-13 days of age. There were no signs of generalized toxicity of short-term DFMO treatment, as body weight gains were largely unaffected over the course of study (through weaning). However, development of peripheral sympathetic neurons was severely retarded by DFMO, with persistent and profound deficits of both cardiac and renal norepinephrine; the catecholamine deficiencies were unrelated to effects on end-organ growth, as cardiac weights were essentially normal whereas kidney weights were adversely affected by DFMO. Development of the adrenal medulla, a peripheral catecholaminergic tissue which displays approximately the same developmental profile as do sympathetic neurons but which does not develop axonal projections, was not slowed by DFMO treatment; similarly, central noradrenergic and dopaminergic neurons, which undergo the majority of axonal outgrowth and synaptogenesis during the second to third postnatal week (just after the period in which polyamines returned to control levels), developed normally as assessed by measurements of transmitter levels, tyrosine hydroxylase activity and synaptosomal uptake of [(3)H]norepinephrine or [(3)H]dopamine. Extension of the period of DFMO treatment and consequent depletion of polyamines into the period in which central synaptogenesis occurs does, however, produce slowing of development of brain catecholamine neuronal projections. Thus, the ODC/polyamine system appears to play a critical postnatal role in catecholamine systems specifically undergoing active synaptogenesis.

Critical periods for the role of ornithine decarboxylase and the polyamines in growth and development of the rat: Effects of exposure to α-difluoromethylornithine during discrete prenatal or postnatal intervals.

The roles of ornithine decarboxylase (ODC) and the polyamines in fetal and neonatal development were examined through the use of α-difluoromethylornithine (DFMO), a specific irreversible inhibitor of ODC. Administration to pregnant rats of 500 mg/kg of DFMO every 12 h for a 4-day period (8 DFMO injections) resulted in fetal and neonatal death; DFMO early in gestation produced fetal resorption whereas late gestational exposure did not compromise fetal viability but instead resulted in a delayed toxic effect, with high mortality in the first postnatal week. Generalized toxicity of DFMO was not apparent in later developmental periods, as 4 days of DFMO treatment begun postnatally did not produce any neonatal death. Shortening the course of gestational DFMO treatment to 2.5 days (5 DFMO injections) also did not adversely affect fetal or neonatal viability and thus permitted identification of critical periods in which various tissues are sensitive to DFMO. Examination of growth patterns of brain, heart and kidney and of neurochemical development of central and peripheral catecholaminergic neurons indicated that different critical periods exist for effects of DFMO on each tissue or even on the various cell types within a tissue. The separable sensitivities were apparent even though the effects of DFMO on ODC and the polyamines for any given treatment period were fairly uniform in all tissues studied. These results indicate that the ODC/polyamine system plays multiple roles in fetal survival and in tissue growth during discrete periods of development; because the time course of cellular maturation differs for each tissue or cell population, DFMO administered during any one brief period can produce organ-specific developmental deficits.

Toxic effects of maternal methadone administration on cardiac development in the neonatal rat: potential participation of altered polyamine levels in growth impairment.

The pattern of development of polyamine levels in hearts of preweanling rats whose mothers received methadone indicated initial deficits in both spermidine and spermine followed by rebound elevations, a pattern consistent with delayed cellular development. Since polyamines are thought to play important roles in nucleic acid and protein synthesis during cellular maturation, these alterations may participate in the retardation of tissue growth seen in the perinatal opiate syndrome.

Ornithine decarboxylase and polyamines in tissues of the neonatal rat: effects of alpha-difluoromethylornithine, a specific, irreversible inhibitor of ornithine decarboxylase.

To evaluate the role of ornithine decarboxylase (ODC) and the polyamines in tissue growth and development, neonatal rats were given daily injections of alpha-difluoromethylornithine, a specific, irreversible inhibitor of ODC. Enzyme activity in brain, heart and kidney was effectively inhibited, leading to prompt reductions in putrescine levels which were apparent throughout the 4-week period of drug treatment. Deficits in spermidine levels appeared within several days and remained significant in all three tissues, although some recovery toward control levels was apparent after 2 weeks postnatally. Spermine levels were not decreased and in some cases were actually increased during the course of alpha-difluoromethylornithine administration; assessment of total organ content of spermine or total polyamines per organ (putrescine + spermidine + spermine) indicated that the tissues were still actively increasing their net polyamine content despite continued inhibition of ODC. Growth of the kidney and brain were affected within several days of commencing alpha-difluoromethylornithine treatment, well before the onset of body weight or heart weight deficits. By 14 days of age and thereafter, animals displayed delayed eye-opening, deficient fur growth and shorter body length. These data suggest that the ODC/polyamine system does serve as a modulator of tissue growth during neonatal mammalian development and that differences exist among various tissues in the degree and time course of dependence of growth on polyamines, particularly putrescine and/or spermidine.

Impaired development of central and peripheral catecholamine neurotransmitter systems in preweanling rats treated with alpha-difluoromethylornithine, a specific irreversible inhibitor of ornithine decarboxylase.

Daily administration of alpha-difluoromethylornithine (DFMO) to neonatal rats results in persistent inhibition of ornithine decarboxylase, depletion of polyamines and rapid onset of brain growth deficits. Animals treated with DFMO displayed marked retardation of synaptic development of catecholaminergic systems in the brain, evidenced by slowed development of synaptosomal uptake of [3H]norepinephrine and of tyrosine hydroxylase activity. Fundamental alterations in brain membrane metabolism also could be detected through measurements of phospholipid incorporation of 33Pi; DFMO suppressed the developmental increments in phospholipid synthesis normally accompanying synaptic outgrowth. Although the content of norepinephrine and dopamine in the brain was unchanged by DFMO, the drug did cause initial reductions, and subsequent elevations, in catecholamine turnover. Effects of DFMO on development of peripheral sympathetic neurons were even more profound, with substantial deficits in norepinephrine content throughout preweanling development, again accompanied by biphasic alterations of turnover. The adrenal medulla, a sympathetic tissue which does not undergo catecholaminergic axonal outgrowth and synaptogenesis, was spared the deleterious effects of DFMO on development. These results support the view that ornithine decarboxylase and the polyamines play an obligatory role in synaptic maturation, with the greatest sensitivity to DFMO-induced alterations occurring during periods of rapid development.

Development of polyamine and biogenic amine systems in brains and hearts of neonatal rats given dexamethasone: role of biochemical alterations in cellular maturation for producing deficits in ontogeny of neurotransmitter levels, uptake, storage and turnover.

Excessive levels of glucocorticoids are thought to interfere with synaptic development in the central nervous system. In the present study, dexamethasone given to newborn rats produced deficits in brain growth associated with shifts in the developmental pattern of the ornithine decarboxylase/polyamine system consistent with delays in cellular maturation. The effects on the brain were of smaller magnitude and shorter duration than those on the heart or on general growth and were indicative of "brain sparing." Although some biochemical indices of synaptic development of central noradrenergic systems ([3H]norepinephrine uptake into synaptosomes) were quantitatively deficient on a whole-brain basis, the reductions never exceeded the magnitude of effect on brain weight; for other indices (transmitter levels, [3H]norepinephrine into synaptic vesicles), there were little or no apparent developmental deficits. Thus, the effects of dexamethasone on synaptic development in the brain may not reflect a specific action of glucocorticoids over and above their more general effects on cellular maturation. In contrast to the lack of specific action on biochemical indices of synaptic outgrowth, neonatal dexamethasone did cause alterations in norepinephrine synthesis and turnover in both central and peripheral sympathetic neurons which could contribute to the physiological and behavioral abnormalities associated with glucocorticoid treatment during development.

Maternal methadone administration: deficit in development of alpha-noradrenergic responses in developing rat brain as assessed by norepinephrine stimulation of 33Pi incorporation into phospholipids in vivo.

The effects of perinatal methadone exposure on the development of noradrenergic responses in the brain were examined by assessing the ability of intracisternally administered norepinephrine to stimulate 33Pi incorporation into phospholipids in vivo; the effect of norepinephrine is mediated by alpha1-receptors juxtaposed to noradrenergic nerve terminals. Although there was no difference in basal (unstimulated) incorporation of 33Pi, a deficit in norepinephrine-induced stimulation of incorporation was found throughout the preweaning period in offspring of dams treated daily with methadone beginning in midgestation. This effect was not seen when methadone was given during the postnatal period. Since perinatal methadone exposure also delays development of presynaptic catecholaminergic nerve terminals in the brain, these results support the view that perinatal exposure to methadone depresses overall central noradrenergic synaptic function; however, the effects on presynaptic development and on receptor-mediated responses appear to be separable in that they display differences in the critical age periods of sensitivity to perturbation by the drug.