Ueber den Einfluss des Antipyrins auf die Stickstoffausscheidung

Ohne Zusammenfassung     

Animal production and wheeze in the Agricultural Health Study: interactions with atopy,asthma, and smoking

Aims: To investigate the role of animal exposures and wheeze, and to assess whether their impact differs among susceptible subgroups, including atopics, asthmatics, and smokers.

Methods: Using the Agricultural Health Study, a cohort of pesticide applicators in Iowa and North Carolina enrolled in 1994–97, wheeze associated with animal production was evaluated and interactions among susceptible subgroups assessed. Logistic regression models were used to examine risk factors for wheeze in the past year among 20 468 farmers.

Results: Individuals raising animals requiring direct contact had the highest odds ratios (OR) for wheeze (OR_dairy = 1.26; OR_eggs = 1.70). A significant dose response was observed for both the number of poultry and the number of livestock on the farm. Farmers who performed veterinary procedures on a daily basis had an OR of 1.51. The odds of wheeze associated with poultry production was greater among atopic than non-atopic individuals. Milking cows daily increased the odds of wheeze in all individuals, with the largest association observed among atopic asthmatic individuals. The impact of dairy, poultry, and egg production varied among smoking groups. Past smokers had the highest odds ratios, followed by never smokers, and then current smokers. The OR_eggs was 2.88 among past smokers but only 1.46 for never smokers. The OR_eggs for current smokers of 0.80 might reflect self selection of exposure among smokers.

Conclusions: Results are consistent with animal production and respiratory symptoms, and suggest that subgroups may respond differently to exposure.

     

Therapie der Glucocorticoid-induzierten Osteoporose mit Alfacalcidol/Kalzium und Vitamin D/Kalzium

Calcium/vitamin D supplementation is generally used as a first step treatment of glucocorticoid-induced osteoporosis (GIOP). The aim of this trial was to compare the efficacy of the D-hormone alfacalcidol with plain vitamin D in patients with established GIOP with or without vertebral fractures. Patients on long-term glucocorticoid-therapy were treated either with 1 microgram alfacalcidol plus 5000 mg calcium (group A: n = 43) or with 1000 IU vitamin D plus 500 mg calcium (group B: n = 42). The two groups were not different in respect to initial characteristics such as age, sex distribution, concomittant diseases, bone mineral density (mean T-score values at lumbar spine and femoral neck: -3.29 and -3.25 resp.), and in the number of prevalent vertebral and non-vertebral fractures. During the 3 years of treatment we found a significant increase in lumbar spine density in group A (+2.0%, p < 0.0001), while no significant changes could be documented in group B at both measuring sites. After 3 years 12 new vertebral fractures had occurred in 10 patients of group A and 21 in 17 patients in group B (ns). Correspondingly we registered a significant decrease of back pain only in group A (p < 0.0001). We conclude that alfacalcidol treatment in superior to plain vitamin D in GIOP.     

Role of the involvement of the reticular formation in the dementia of Parkinson's disease

A post mortem study of 14 cases of Parkinson's disease was reported. Seven patients were mentally deteriorated and 7 were not, retrospectively. The semiquantitative study of the cortical lesions of senile dementia of Alzheimer type did not show any recognizable difference between the 2 groups. A greater degree of neuronal cell loss in the nucleus basalis of Meynert in the mentally deteriorated group was confirmed. The incidence of Lewy bodies in the brain stem reticular formation was remarkably increased in the mentally deteriorated group. A study of the reticular formation, including the raphe nuclei and the magnocellular nuclei of mid pons and upper medulla, revealed a significant higher incidence of Lewy bodies throughout the whole reticular formation in the mentally deteriorated group. The possible role of the lesions of the ascending reticular activating system in the mental deterioration is discussed.     

Selective nucleoside triphosphate diphosphohydrolase-2 (NTPDase2) inhibitors: nucleotide mimetics derived from uridine-5'-carboxamide

Ecto-nucleoside triphosphate diphosphohydrolases (E-NTPDases, subtypes 1, 2, 3, 8 of NTPDases) dephosphorylate nucleoside tri- and diphosphates to the corresponding di- and monophosphates. In the present study we synthesized adenine and uracil nucleotide mimetics, in which the phosphate residues were replaced by phosphonic acid esters attached to the nucleoside at the 5'-position by amide linkers. Among the synthesized uridine derivatives, we identified the first potent and selective inhibitors of human NTPDase2. The most potent compound was 19a (PSB-6426), which was a competitive inhibitor of NTPDase2 exhibiting a K i value of 8.2 microM and selectivity versus other NTPDases. It was inactive toward uracil nucleotide-activated P2Y 2, P2Y 4, and P2Y 6 receptor subtypes. Compound 19a was chemically and metabolically highly stable. In contrast to the few known (unselective) NTPDase inhibitors, 19a is an uncharged molecule and may be perorally bioavailable. NTPDase2 inhibitors have potential as novel cardioprotective drugs for the treatment of stroke and for cancer therapy.     

US assessment of estrogen-responsive organ growth among healthy term infants: piloting methods for assessing estrogenic activity

Background  

A mother’s circulating estrogen increases over the third trimester, producing physiological effects on her newborn that wane postnatally. Estrogenization might be prolonged in newborns exposed to exogenous estrogens, such as isoflavones in soy formula.     

Parameterizing dose-response models to estimate relative potency functions directly

Many comparative analyses of toxicity assume that the potency of a test chemical relative to a reference chemical is constant, but employing such a restrictive assumption uncritically may generate misleading conclusions. Recent efforts to characterize non-constant relative potency rely on relative potency functions and estimate them secondarily after fitting dose-response models for the test and reference chemicals. We study an alternative approach of specifying a relative potency model a priori and estimating it directly using the dose-response data from both chemicals. We consider a power function in dose as a relative potency model and find that it keeps the two chemicals' dose-response functions within the same family of models for families typically used in toxicology. When differences in the response limits for the test and reference chemicals are attributable to the chemicals themselves, the older two-stage approach is the more convenient. When differences in response limits are attributable to other features of the experimental protocol or when response limits do not differ, the direct approach is straightforward to apply with nonlinear regression methods and simplifies calculation of simultaneous confidence bands. We illustrate the proposed approach using Hill models with dose-response data from U.S. National Toxicology Program bioassays. Though not universally applicable, this method of estimating relative potency functions directly can be profitably applied to a broad family of dose-response models commonly used in toxicology.