Six million children live in poverty in America's inner cities. These children are at high risk of exposure to pesticides that are used extensively in urban schools, homes, and day-care centers for control of roaches, rats, and other vermin. The organophosphate insecticide chlorpyrifos and certain pyrethroids are the registered pesticides most heavily applied in cities. Illegal street pesticides are also in use, including tres pasitos (a carbamate), tiza china, and methyl parathion. In New York State in 1997, the heaviest use of pesticides in all counties statewide was in the urban boroughs of Manhattan and Brooklyn. Children are highly vulnerable to pesticides. Because of their play close to the ground, their hand-to-mouth behavior, and their unique dietary patterns, children absorb more pesticides from their environment than adults. The long persistence of semivolatile pesticides such as chlorpyrifos on rugs, furniture, stuffed toys, and other absorbent surfaces within closed apartments further enhances urban children's exposures. Compounding these risks of heavy exposures are children's decreased ability to detoxify and excrete pesticides and the rapid growth, development, and differentiation of their vital organ systems. These developmental immaturities create early windows of great vulnerability. Recent experimental data suggest, for example, that chlorpyrifos may be a developmental neurotoxicant and that exposure in utero may cause biochemical and functional aberrations in fetal neurons as well as deficits in the number of neurons. Certain pyrethroids exert hormonal activity that may alter early neurologic and reproductive development. Assays currently used for assessment of the toxicity of pesticides are insensitive and cannot accurately predict effects to children exposed in utero or in early postnatal life. Protection of American children, and particularly of inner-city children, against the developmental hazards of pesticides requires a comprehensive strategy that monitors patterns of pesticide use on a continuing basis, assesses children's actual exposures to pesticides, uses state-of-the-art developmental toxicity testing, and establishes societal targets for reduction of pesticide use.

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Alzheimer's disease (AD) is a major cause of dementia. Characteristic neuropathological features of AD include neurofibrillary tangles, senile plaques, amyloid angiopathy and microvascular atrophy. The ultra-structure of the microvascular atrophy in AD and its pathogenetic significance have not been defined. This report presents an analysis of ultrastructural and morphometric features in the cerebral microvasculature of five brain biopsy specimens from AD patients. The cerebral microvasculature normally constitutes the blood-brain barrier (BBB), characterized by interendothelial tight junctions, few pinocytotic vesicles and high mitochondrial content in endothelial cells. In the AD brain biopsy tissue analyzed in the present article, data for endothelial cells were expressed as percentage of cytoplasmic area occupied by the respective organelles. The values for vesicular content ranged from 0.49% to 1.17% and were inversely correlated with mitochondrial content, which ranged from 7.04% to 2.88%. These results indicate decreased mitochondrial content and increased pinocytotic vesicles as compared to values obtained previously in endothelium from multiple sclerosis patients and in laboratory animals. Other findings such as accumulation of collagen in vascular basement membranes and focal necrotic changes in endothelial cells are further indications of BBB disruption. These data, together with earlier reports, suggest that dysfunction of the BBB is a characteristic feature of AD.

Brain capillaries were analyzed morphometrically for alterations in organelle distribution and density in biopsy samples of central nervous system tissue from seven patients diagnosed as having chronic progressive multiple sclerosis. Data were expressed as percentage of endothelial cytoplasm occupied by the respective organelles. The density of pinocytotic vesicles in endothelium ranged from 0.53% within normal-appearing parenchyma to 1.2% in gliotic areas. For mitochondria the values ranged from 10.87% in normal areas to 4.72% in the same respective samples. Thus, an inverse correlation between vesicular and mitochondrial content was observed. These findings suggest that endothelial cells in gliotic areas are similar to endothelial cells of the systemic circulation in their mitochondrial content and pinocytotic activity. Interendothelial junctions in capillaries of all areas examined appeared normal. Additional evidence for a continuous blood-brain barrier anomaly in multiple sclerosis was the accumulation of perivascular fibrin, suggesting an increase in microvascular permeability. Perivascular collagen deposits, degenerative changes in pericytes and astrocytic swelling were also indicators of an increase in blood-brain barrier permeability. Taken together with previous data from experimental autoimmune encephalomyelitis, the present findings in chronic silent multiple sclerosis lesions suggest that central nervous system endothelial cells show persistent abnormalities of the blood-brain barrier, even in the absence of active inflammation.