The release of excitatory amino acids,dopamine, and potassium following transplantation of embryonic mesencephalic dopaminergic grafts to the rat striatum,and their effects on dopaminergic neuronal survival in vitro

A major limitation to the effectiveness of grafts of fetal ventral mesencephalic tissue for parkinsonism is that about 90-95% of grafted dopaminergic neurones die. In rats, many of the cells are dead within 1 day and most cell death is complete within 1 week. Our previous results suggest that a major cause of this cell death is the release of toxins from the injured CNS tissue surrounding the graft, and that many of these toxins have dissipated within 1 h of inserting the grafting cannula. In the present experiments we measured the change over time in the concentration of several potential toxins around an acutely implanted grafting cannula. We also measured the additional effect of injecting suspensions of embryonic mesencephalon, latex microspheres, or vehicle on these concentrations. Measurements of glutamate, aspartate, and dopamine by microdialysis showed elevated levels during the first 20-60 min, which then declined to baseline. In the first 20 min glutamate levels were 10.7 times, aspartate levels 5 times, and dopamine levels 24.3 times baseline. Potassium levels increased to a peak of 33 +/- 10.6 mM 4-5 min after cannula insertion, returning to baseline of <5 mM by 30 min. Injection of cell suspension, latex microspheres, or vehicle had no significant effect on these levels. We then assayed the effect of high concentrations of glutamate, aspartate, dopamine, and potassium on dopaminergic neuronal survival in E14 ventral mesencephalic cultures. In monolayer cultures only dopamine at 200 microM showed toxicity. In three-dimensional cultures only the combination of raised potassium, dopamine, glutamate, and aspartate together decreased dopaminergic neuronal survival. We conclude that toxins other than the ones measured are the main cause of dopaminergic cell death after transplantation, or the effects of the toxins measured are enhanced by anoxia and metabolic challenges affecting newly inserted grafts.     

Pregnancy outcomes among farming households of Nueva Ecija with conventional pesticide use versus integrated pest management

A retrospective cohort study was conducted to compare pregnancy outcomes in farming households that used pesticides conventionally with those that practiced integrated pest management (IPM) in Nueva Ecija, Philippines, in the period 1998-1999. Conventional pesticide users (CPUs) were defined as pesticide appliers who used pesticides routinely and regularly, whereas users of IPM were those who used pesticides as necessary, and on economically injured crop areas only. The data sets were subjected to the chi-square test of association, Fisher's exact probability test, and logistic regression analysis. At a significance level at 0.05, spontaneous abortion occurred significantly more often among the 345 CPU households than among the 331 IPM households (adjusted risk ratio 6.17). Likewise, birth defects were significantly more common in the CPU group (adjusted risk ratio 4.56). Thus, people of reproductive age who plan to have children should avoid any use of pesticides.     

The health of immigrant women: Queensland women from the former Yugoslavia

A study of the social and health status of women from the former Yugoslavia was conducted in Queensland, Australia. Study participants were predominantly refugee women who had migrated to Australia between 1991 and 1996. A significant number of the women rated their health status as poor or fair. Most women did not perceive any change in health following migration, but more felt that their health had deteriorated than improved. Applying a social model of health, we explored the social contexts of countries of origin and destination that impact on women's health. We analyze how preimmigration trauma, settlement problems, health risk behaviors, and participation in screening programs affect women's health status and health needs. Data analysis indicated that government and nongovernment services can reduce the impact of preimmigration experience on health risk behaviors and poor health outcomes only to a limited degree. Since the low socioeconomic status of immigrants following immigration was identified by women as a main contributing factor to their poor health status, government support in tackling structural barriers in accessing the Australian labor market is essential to achieve positive health outcomes.     

Type 2 diabetes, APOE gene, and the risk for dementia and related pathologies: The Honolulu-Asia Aging Study

Type 2 diabetes may be a risk factor for dementia, but the associated pathological mechanisms remains unclear. We evaluated the association of diabetes alone or combined with the apolipoprotein E (APOE) gene with incident dementia and neuropathological outcomes in a population-based cohort of 2,574 Japanese-American men enrolled in the Honolulu-Asia Aging Study, including 216 subjects who underwent autopsy. Type 2 diabetes was ascertained by interview and direct glucose testing. Dementia was assessed in 1991 and 1994 by clinical examination and magnetic resonance imaging and was diagnosed according to international guidelines. Logistic regression was used to assess the RR of developing dementia, and log-linear regression was used to estimate the incident rate ratio (IRR) of neuropathological outcomes. Diabetes was associated with total dementia (RR 1.5 [95% CI 1.01-2.2]), Alzheimer's disease (AD; 1.8 [1.1-2.9]), and vascular dementia (VsD; 2.3 [1.1-5.0]). Individuals with both type 2 diabetes and the APOE epsilon4 allele had an RR of 5.5 (CI 2.2-13.7) for AD compared with those with neither risk factor. Participants with type 2 diabetes and the epsilon4 allele had a higher number of hippocampal neuritic plaques (IRR 3.0 [CI 1.2-7.3]) and neurofibrillary tangles in the cortex (IRR 3.5 [1.6-7.5]) and hippocampus (IRR 2.5 [1.5-3.7]), and they had a higher risk of cerebral amyloid angiopathy (RR 6.6, 1.5-29.6). Type 2 diabetes is a risk factor for AD and VsD. The association between diabetes and AD is particularly strong among carriers of the APOE epsilon4 allele. The neuropathological data are consistent with the clinical results.     

Soy-based formulae and infant growth and development: a review

Soy-based infant formulae, initially developed for infants who were lactose intolerant or allergic to cow's milk-based formulae, now account for >25% of the infant formulae sold in the United States. Formulations have changed over the years to improve digestibility, the stability and availability of minerals, and protein quality. Recent concerns have been raised regarding the phytoestrogenic isoflavone content of soy-based formulae. A systematic review of the literature was conducted to evaluate various measures of infant health and development in clinical studies comparing modern soy-based formulae with other diets and to document areas in which further research seems warranted. Results suggest that modern soy-based formulae support normal growth and nutritional status in healthy term infants in y 1 of life. However, there are very limited data on sexual and reproductive development or outcomes such as immune function, visual acuity/cognitive development and thyroid function. Available data do not provide evidence of meaningful differences in timing of maturation, sexual development or fertility in adolescents or adults. Nonetheless, given evidence suggesting that early exposure to soy and/or isoflavones might have long-term effects, further research following infants fed soy-based formulae into adulthood is warranted.     

Volume and differentiation of striatal grafts in rats: relationship to the number of cells implanted

A growing body of evidence suggests that graft-mediated functional recovery in animal models of Huntington's disease is influenced by the morphology of the striatal grafts. Various parameters, including embryonic dissection, tissue preparation, and surgical delivery into the brain, have been investigated with the aim of increasing the proportion of the grafts comprising striatum-like tissue. While growing evidence suggests that implants derived from the selective dissection of the lateral ganglionic eminence (LGE) contain more striatal tissue, the relationship between the quantity of LGE tissue implanted and the striatum-like proportion of the resultant grafts has not been formally investigated. In this study the volume of striatum-like tissue within the grafts did not increase in a linear manner with increasing numbers of cells implanted. The proportion of the grafts that comprised the striatum-like patch compartment or P-zone remained constant after an initial rapid increase as the number of LGE cells implanted was increased. These results have important practical implications in determining the optimum number of LGE cells to implant and hence in the design of any surgical protocol for the clinical application of this technique.     

Measuring the impact of health problems among adults with limited mobility in Thailand: further validation of the Perceived Impact of Problem Profile

Background  

The Perceived Impact of Problem Profile (PIPP) was developed to provide a tool for measuring the impact of a health condition from the individual's perspective, using the ICF model as a framework. One of the aims of the ICF is to enable the comparison of data across countries, however, relatively little is known about the subjective experience of disability in middle and low-income countries. The aim of this study was to assess the validity of the Perceived Impact of Problem Profile (PIPP) for use among adults with a disability in Thailand using Rasch analysis.     

Boundary breaches: the body, sex and sexuality after stoma surgery

People with limited or no bladder or bowel control, who have had a stoma to manage elimination, have a particular awareness of the proximity of the sites of pleasure and excretion. Drawing on interviews and related ethnography conducted in Australia from 1998 to 2001, this paper explores how men and women with permanent continence problems negotiate their sexuality around their bodily unreliability. Pleasurable sex, idealized, involves losing control. People who are incontinent or rely on a stoma, however, must monitor their bladder and bowel, disguising the stoma and bag and controlling their body in sex as in other circumstances. The need to negotiate bodily boundaries with established partners, or to disclose to new sexual partners, results in self-consciousness and social unease, and people need to reconstruct notions of privacy and dignity so that breaches in bodily control do not undermine the sexual relationship. For many, the stoma undermines self-esteem and body image, while its management confuses the status of the individual as "normal" and the partner as carer or lover.     

Training specificity, graft development and graft-mediated functional recovery in a rodent model of Huntington's disease

Neuronal function and morphology are affected by the environment and the behavioral experience. Here we report on the effects of differential training protocols on the development and the functional recovery mediated by intrastriatal striatal grafts. Rats were trained exclusively on the left or the right paw to perform on the skilled staircase task before being lesioned unilaterally in the dorsal striatum with quinolinic acid. E15 whole ganglionic eminence suspension grafts were implanted into the lesioned striatum. Subsequent testing probed unilateral performance of the affected contralateral paw, as well as bilateral performance. The grafted animals were initially as impaired as the lesioned, but partially recovered their performance with additional training. Grafted animals with appropriate previous experience initially performed better on the staircase test, but the advantage was transient. Furthermore, the grafted animals performed better with their affected paw under forced choice than under conditions when both paws were simultaneously probed. Improvements of the grafted animals were also observed on tests of forelimb akinesia and asymmetry. Morphological data suggest that the training conditions influenced the development specifically of striatal-like, but not of non-striatal like, neurones within the grafts. The grafts were smaller containing less striatal-like neurones in animals that were trained on the contralateral side prior to lesioning and grafting. The results support the hypothesis that unilateral training sensitizes the striatum that subserves the motor learning, leading to exacerbated excitotoxic lesions and to an environment less conducive for graft development.     

Frontal-striatal disconnection disrupts cognitive performance of the frontal-type in the rat

The prefrontal cortex is considered to provide executive control of response selection and planning in diverse cognitive tasks, translated into action via descending subcortical projections (or 'loops') through the basal ganglia. We have used a disconnection strategy to demonstrate first that bilateral fronto-striatal disconnection disrupts rats' abilities to perform delayed alternation, the classic test of prefrontal function in rats and monkeys, and second that crossed unilateral cortical and striatal lesions on opposite sides similarly disrupt rats' abilities to perform the same cognitive task. We found that effective disconnection requires interruption of interhemispheric transfer, achieved by transection of the anterior corpus callosum. This produces a moderate deficit in its own right, which is not exacerbated by additional prefrontal and striatal lesions in one hemisphere. Conversely, the animals are significantly more impaired after crossed prefrontal and striatal lesions of similar total magnitude. The results demonstrate than an intact cortico-striatal pathway is necessary to sustain performance on a classical prefrontal task, and provide a model within which to assess circuit reconstruction with novel cell therapies for brain repair.