Smoking and Parkinson''s disease: a dose-response relationship

BACKGROUND: Previous studies questioned the link between early childhood anemia and detrimental child development. OBJECTIVE: A population-based study was conducted to examine the association between early childhood anemia and mild or moderate metal retardation at 10 y of age. DESIGN: The present study linked early childhood nutrition data collected by the Special Supplemental Program for Women, Infants, and Children (WIC) and school records. Hemoglobin values were used to determine the relation between anemia in early life and children's placement in special education classes for mild or moderate mental retardation. Subjects were all participants in the WIC program. A computer program was used to link data from birth, WIC, and school records. RESULTS: Logistic regression showed an increased likelihood of mild or moderate mental retardation associated with anemia, independent of birth weight, maternal education, sex, race-ethnicity, the mother's age, or the child's age at entry into the WIC program. CONCLUSION: These findings support the proposition that efforts to prevent mild and moderate mental retardation should include providing children with adequate nutrition during early childhood.     

Stimulation of the extracellular signal-regulated kinase 1/2 pathway by human beta-3 adrenergic receptor: new pharmacological profile and mechanism of activation

(-)Deprenyl is an irreversible inhibitor of monoamine oxidase B (MAO-B) frequently used as an adjunct therapy in the treatment of Parkinson's Disease. Recent evidence, however, has found that deprenyl's metabolites are associated with an antiapoptotic action within certain neuronal populations. Interestingly, deprenyl's antiapoptotic actions appear not to depend upon the inhibition of MAO-B. Due to a paucity of information surrounding (-)deprenyl's ability to spare neurons in vivo, a series of studies was conducted to further investigate this phenomenon within an apoptotic neuronal death model: kainic acid induced excitotoxicity. Results indicated that (-)deprenyl increased hippocampal neuronal survival compared to saline-matched controls following kainic acid insult. Furthermore, it was discovered that (-)deprenyl treatment could be stopped 14 days following CNS insult by kainate, with evidence of neuronal sparing still present by day 28. In open-field locomotor activity testing of kainate-treated animals, those given subsequent (-)deprenyl treatment showed habituation curves similar to control subjects, while saline-treated animals did not. Given deprenyl's antiapoptotic actions, it is proposed that (-)deprenyl may be beneficial in the treatment of a variety of neurodegenerative diseases where evidence of apoptosis exists, such as Parkinson's and Alzheimer's Disease, by slowing the disease process itself.     

Deficiency in collagen and fibronectin phagocytosis by human buccal mucosa fibroblasts in vitro as a possible mechanism for oral submucous fibrosis

Oral submucous fibrosis (OSF), a chronic oral mucosal condition commonly found in south Asians, is a disorder characterized by a quantitative as well as a qualitative alteration of collagen deposition within the subepithelial layer of the oral mucosa. Since degradation of collagen by fibroblast phagocytosis is an important pathway for physiological remodelling of soft connective tissues, we have investigated phagocytosis of collagen- and fibronectin-coated latex beads by fibroblast cultures with an in vitro model system. Coated fluorescent latex beads were incubated with human oral mucosa fibroblasts and the fluorescence associated with internalized beads was measured by flow cytometry. Cells from normal tissues that had been incubated with beads for 16 h contained a mean of 75% collagen phagocytic cells and 70% fibronectin phagocytic cells; however, about 15% and 10% of phagocytic cells individually contained more than twice the mean number of beads per cell. In contrast, cells from OSF tissues exhibited a 40% reduction of the proportions of collagen phagocytic cells (mean=35%) and a 48% decrease of the proportions of fibronectin phagocytic cells (mean=22%), none of the cells having a high number of beads as compared to normal fibroblasts. OSF lesions appear to contain fibroblasts with marked deficiencies in collagen and fibronectin phagocytosis. To investigate if inhibition of phagocytosis could be demonstrated in vitro, normal fibroblast cultures were incubated with areca nut alkaloids (arecoline, arecaidine). The cultures had a dose-dependent reduction in the proportions of phagocytic cells. On the other hand, corticosteroid used in the treatment of OSF exhibited a dose-dependent enhancement in the proportion of phagocytic cells. Therefore, our hypothesis for OSF, although oversimplified, is that betel nut alkaloids (arecoline, arecaidine) inhibit fibroblast phagocytosis and this provides a mechanism for the development of OSF. The benefit of a local intralesional injection of corticosteroid is also possibly, at least in part, through an enhancement of fibroblast collagen phagocytosis.     

Inhibition of metastases by anticoagulants

Medicare spends more than $200 billion a year; the politics surrounding the Medicare program cannot be fully understood without an adequate appreciation of that fact. An understanding of the political economy of Medicare is perhaps best achieved by thinking along three dimensions: (1) Medicare as redistributive politics; (2) Medicare as special-interest politics; and (3) Medicare as distributive politics. Seeing the extent to which Medicare policies flow from these political processes makes clear that Medicare reform and broader political reform are, at some level, inseparable and indistinguishable.     

Urinary lithiasis: epidemiology and physiopathology

Urolithiasis has an incidence of about 12% in men and about 5% in women before the age of 70 years. Several epidemiological factors are involved in the predisposition to the urinary stone disease, notably: age, sex, race, climate, geography, profession, social class, nutritional factors and inherent genetic particularities. A number of physicochemical mechanisms govern lithogenesis, passing from saturation and supersaturation of urine to nucleation, crystallization and crystal growth to clinically significant sizes when the inhibition mechanisms are overwhelmed or absent. Generally urinary stone are of diverse aetiologies, that can essentially be grouped in calcium, uric acid, cystine and magnesium ammonium phosphate stones with subgroups in relation to the varied pathophysiological mechanisms involved in each case.     

A study of injected dose for brain mapping on the ECAT HR+: activation maps for a parametric verbal working memory task

The success of the 15O-water PET technique to localize statistically significant changes in regional cerebral blood flow is dependent on factors such as the activity level injected and the magnitude of the flow change. Undetectable changes may occur if insufficient activity is injected leading to high levels of statistical noise or the task performed results in only small changes in blood flow. To explore the relationship between injected activity and statistical significance, we performed a series of studies with the ECAT EXACT HR+, a high resolution PET tomograph. A parametric verbal working memory task (the N-back task) was selected to examine the relationship between regional cerebral blood flow and working memory load across a range of injected doses of 15O-water. At each activity level the volunteers were required to perform four different levels of the N-back task, a task in which a letter displayed on a monitor is matched with the letter displayed N letters previously. With increasing N, this task places increased load on working memory. For this study, 5, 10, and 15 mCi of 15O-water were injected into nine normal volunteers. The complete sequence of four tasks (N = 0, 1, 2, and 3) at three activity levels was repeated twice, for a total of 24 injections of 15O-water. We show that the peak count rate performance for the HR+ is approached at injected activity levels of 15O-water around 15 mCi. For this particular choice of N-back task, robust activation maps can nevertheless be obtained with as little as 5 mCi injected dose.