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Cooperative ratiometric chemosensors: pinwheel receptors with an integrated fluorescence system.

The synthesis and fluorescent properties of a second generation cooperative chemical sensor are described. The sensor has two interacting binding pockets for cooperative recognition of two analytes. Cooperative binding activates a ratiometric fluorescent response via formation of an excimer. Binding was characterized by NMR, absorption, and fluorescence spectroscopy. The advantages of separating the recognition elements from the fluorescent response elements are discussed.

Acetylene↗

Metabolic control in integrated biochemical systems.

Traditional analyses of the control and regulation of steady-state concentrations and fluxes assume the activities of the enzymes to be constant. In living cells, a hierarchical control structure connects metabolic pathways to signal-transduction and gene-expression. Consequently, enzyme activities are not generally constant. This would seem to compromise analyses of control and regulation at the metabolic level. Here, we investigate the concept of metabolic quasi-steady state kinetics as a means of applying metabolic control analysis to hierarchical biochemical systems. We discuss four methods that enable the experimental determination of metabolic control coefficients, and demonstrate these by computer simulations. The best method requires extra measurement of enzyme activities, two others are simpler but are less accurate and one method is bound only to work under special conditions. Our results may assist in evaluating the relative importance of transcriptomics and metabolomics for functional genomics.

Enzymes↗

[From "Burden of disease" research to the conception of an integrated care system for substance abuse in Ontario].

The paradigm of evidence-based medicine has become one of the building blocks of modern health policy in established market economies. Based on this paradigm, a monitoring system for treatment of substance abuse has been developed in the Canadian province of Ontario. This monitoring system comprises four main elements: availability of treatment places, utilization of specialized health services, costs of treatment and outcome indicators. The paper discusses difficulties in implementing the system and gives some indications on future developments.

Ambulatory Care Facilities↗

Physical activity, fitness and integrated antioxidant system in healthy active elderly women.

We have related the oxidative stress and antioxidant defence system to maximal oxygen consumption (VO2max) and physical activity in elderly women. Twenty-nine community dwelling, healthy, active women aged 66-82 years participated in this study. Physical activity was measured by a questionnaire and expressed using two physical activity indices: mean habitual daily energy expenditure (MHDEE) and daily energy expenditure corresponding to leisure time sports activities (Sports activity index). Malondialdehyde (MDA), plasma total antioxidant status (TAS), the red blood cell (RBC) superoxide dismutase (SOD) and glutathione peroxidase (GPX) as well as serum GPX activities were determined under resting conditions. MDA was correlated positively with VO2max (r = 0.42), while RBC GPX was significantly negatively associated with VO2max (r =-0.39), MHDEE (r=-0.38) and sports activity index (rho=-0.36). Our data suggest that in healthy active older women the relationship between physical activity/fitness and antioxidant defence system may be complex, and that for some parameters an unfavourable influence of strenuous exercise may exist. The findings of this cross-sectional design need to be supported in further prospective studies before the associations are accepted as real.

Aged↗

Development of an integrated microanalytical system for analysis of lead in saliva and linkage to a physiologically based pharmacokinetic model describing lead saliva secretion.

There is a need to develop reliable portable analytical systems for biomonitoring lead (Pb) in noninvasively collected saliva samples. In addition, appropriate pharmacokinetic analyses are used to quantitate systemic dosimetry based on the saliva Pb concentrations. A portable microfluidics/electrochemical device was developed for the rapid analysis of Pb based on square wave anodic stripping voltammetry, in which a saliva sample flows over an electrode surface, Pb2+ is chemically reduced and accumulated, and the electric potential of the electrode scanned. The system demonstrates a good linear response over a broad Pb concentration range (1-2000 ppb). To evaluate the relationship between saliva and blood Pb, rats were treated with single oral doses ranging from 20 to 500 mg Pb/kg of body weight, and 24 hours later were administered pilocarpine, a muscarinic agonist to induce salivation. To correlate saliva levels with internal dose, blood and saliva were collected and quantitated for Pb by inductively coupled plasma-mass spectrometry (ICP-MS) and by the microanalytical system. The quantitation with the microanalytical system was slightly less (approximately 75-85%) than with ICP-MS; however, the response was linear, with concentration suggesting that it can be used for the quantitation of salivary Pb. To facilitate modeling, a physiologically based pharmacokinetic (PBPK) model for Pb was modified to incorporate a salivary gland compartment. The model was capable of predicting blood and saliva Pb concentration based on a limited data set. These results are encouraging, suggesting that once fully developed the microanalytical system coupled with PBPK modeling can be used as important tools for real-time biomonitoring of Pb for both occupational and environmental exposures.

Animals↗

Pilot testing of dissolved air flotation (DAF) in a highly effective coagulation-flocculation integrated (FRD) system.

Factors of pretreatment coagulation/flocculation units were studied using raw water of low temperature and low turbidity. Aluminum sulfate (AS) and selected polyaluminium chlorides (PACls) were all effective in the DAF process when used under favorable conditions of coagulant addition, coagulation, flocculation and flotation units. Compared with the AS coagulant, PACls, at lower dosage, could give the same effective performance even with shorter coagulation/flocculation time or lower recycle ratio during the treatment of cold water. This is attributed to the higher-charged polymeric Al species, and the lower hydrophilic and more compact flocculated flocs of PACl coagulant. Based on results of pilot experiments, the goal of FRD system can be achieved by combining a DAF heterocoagulation reactor with PACl coagulant (F), an efficient flocculation reactor (R), as well as an economical auto-dosing system (D).

Air↗

Evaluation of the CTrach--an intubating LMA with integrated fibreoptic system.

BACKGROUND: The laryngeal mask airway CTrach (CTrach) is a variant of the intubating laryngeal mask airway. It provides visualization of the larynx during intubation and is designed to increase the success rates of ventilation and tracheal intubation. METHODS: Sixty healthy anaesthetized and paralysed patients with normal airways were studied. The success rates of ventilation and intubation using CTrach were determined. Laryngeal view scoring ranged from grade I (full view of arytenoids and glottis), II (arytenoids and glottis partly visible), III (view of arytenoids, glottis or epiglottis blurred, or view clear with only epiglottis visible) to IV (no part of larynx identifiable). Adjusting manoeuvres were undertaken to improve the laryngeal view in grades II or worse. RESULTS: CTrach insertion and ventilation was possible in all patients. Initial views were scored as grade I in 22 (36.7%), grade II in 14 (23.3%), grade III in 7 (11.7%) and grade IV in 17 (28.3%) patients. Adjusting manoeuvres were undertaken in 38 patients with grade II and worse (63.3%), resulting in improved views of grade I in 33 (55.0%), grade II in 18 (30.0%), grade III in 4 (6.7%) and grade IV in 5 (8.3%) patients. Tracheal intubation was successful in 58 (96.6%) patients at first attempt and in one at second. Tracheal intubation failed once. CONCLUSIONS: In 60 patients with normal airways, the CTrach was used successfully for ventilation, with successful tracheal intubation in 59 patients. Tracheal intubation can be successful despite grade III or IV views.

Adolescent↗

Clinical significance of the association of the Von Hippel-Lindau disease with pheochromocytoma and pancreatic apudoma.

Von Hippel-Lindau disease (VHLD) is a rare disorder known to occur with pheochromocytoma. We report a case with this association and also with pancreatic apudoma. We believe that this is the fifth reported case of this triad, which represents an overlap in the multiple endocrine neoplasia (MEN) classification. Many recent reports of overlap of MEN syndromes challenge the validity of this classification. New understanding of the embryologic origin of cells of endocrine organs has led to the elucidation of the APUD (amine precursor uptake and decarboxylation)-neuroendocrine system. Integration of the APUD system may be important to understanding the pathogenesis of the MEN-like syndromes as well as their relationship to the neurocutaneous syndromes. Any endocrine tumor or neurocutaneous syndrome should be evaluated to exclude a spectrum of possible associations.

Adult↗