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At least 811 records · Page 45Linked to original sources
PubMed2002

Optical chloride sensor based on dimer-monomer equilibrium of indium(III) octaethylporphyrin in polymeric film.

A novel transduction chemistry for preparing optical anion-selective polymeric films that respond reversibly and selectively to chloride ion activity is demonstrated. The chloride sensors are prepared by casting thin (5-10 microm) plasticized PVC films containing indium(III) octaethylporphyrin hydroxide, along with optimized levels of a lipophilic tetraphenylborate salt, onto glass slides. When bathed in low-pH buffered solutions void of chloride, the porphyrin species spontaneously forms a hydroxide ion-bridged dimer, with the added lipophilic borate species serving as the counteranion for this complex. The maximum for the Soret absorption band of this dimeric species is shifted to 390 nm, from 410 nm for the initial monomeric porphyrin. Increases in chloride ion levels in the bathing solution results in chloride extraction and ligation to the In(III) center, and concomitant breaking of the dimer into monomeric porphyrin species, yielding a decrease in absorbance at 390 nm and an increase in optical signal at 410 nm. Under optimized conditions, optical selectivity coefficients toward chloride over a wide range of other anions (NO3-, ClO4-, SCN-, SO4(2-), F-, Br-, H2PO4-) are measured to be < 10(-3). Of all anions tested, only salicylate yields a slightly greater response than chloride. This selectivity is shown to be adequate for reversible and accurate sensing of chloride levels in diluted serum samples.

Animals↗
PubMed1985

Calmodulin: calcium, potassium, and magnesium ion multiple equilibria and kinetics for interconversion, including the effect of repeated stimulation.

Using computer simulations, with realistic values for the intrinsic thermodynamic binding constants and kinetic on and off rate constants at the four metal-binding sites, the calmodulin molecule is shown to have been optimally adjusted by evolution for biological function. Despite a very large number of potential molecular states, depending upon occupation by potassium, calcium, or magnesium ions, the system restricts itself to a small number of physiologically-significant equilibrium species. It appears to possess built-in triggers for biological processes, with rapid (approximately 20 ms time-scale), step-function shaped, changes of the populations of the CMKK, CMMK, CKKK, CMMM (and CCKK) states. The time-response of calmodulin to periodic changes in ionic levels (2 and 5 s-1) makes it quite adequate for repeated stimulations. In short, calmodulin appears as a very selective information transmitter at the molecular level.

Binding Sites↗
PubMed1998

Ligand-binding studies: old beliefs and new strategies.

Ligand-binding studies remain a very popular technique among many experimentalists. As far as equilibrium experiments are concerned, saturation and displacement curves are commonly performed for simplicity, convenience or for the sake of tradition. However, alternative protocols, such as 'mixed'-type protocols or multiligand experiments, are also possible. Indeed, there are cases where kinetic experiments, usually considered a 'second-choice' experiment, might have a superior resolving power compared to equilibrium ones. A combination of equilibrium and kinetic experiments might be a powerful solution to overcome limits and shortcomings of each specific technique and is discussed in this issue by G. Enrico Rovati. Thus, a careful choice of the design, a protocol optimization and a computerized analysis of the data can yield a dramatic improvement in the precision of the parameter estimation over more conventional approaches.

Computer Simulation↗
PubMed2003

Aromatic thiol pKa effects on the folding rate of a disulfide containing protein.

The production of proteins via recombinant DNA technology often requires the in vitro folding of inclusion bodies, which are protein aggregates. To create a more efficient redox buffer for the in vitro folding of disulfide containing proteins, aromatic thiols were investigated for their ability to increase the folding rate of scrambled RNase A. Scrambled RNase A is fully oxidized RNase A with a relatively random distribution of disulfide bonds. The importance of the thiol pK(a) value was investigated by the analysis of five para-substituted aromatic thiols with pK(a) values ranging from 5.2 to 6.6. Folding was measured at pH 6.0 where the pK(a) value of the thiols would be higher, lower, or equal to the solution pH. Thus, relative concentrations of thiol and thiolate would vary across the series. At pH 6.0, the aromatic thiols increased the folding rate of RNase A by a factor of 10-23 over that observed for glutathione, the standard additive. Under optimal conditions, the apparent rate constant increased as the thiol pK(a) value decreased. Optimal conditions occurred when the concentration of protonated thiol in solution was approximately 2 mM, although the total thiol concentration varied considerably. The importance of the concentration of protonated thiol in solution can be understood based on equilibrium effects. Kinetic studies suggest that the redox buffer participates as the nucleophile and/or the center thiol in the key rate determining thiol disulfide interchange reactions that occur during protein folding. Aromatic thiols proved to be kinetically faster and more versatile than classical aliphatic thiol redox buffers.

Buffers↗
PubMed1998

Domain swapping in G-protein coupled receptor dimers.

Computer simulations were performed on models of the beta2-adrenergic receptor dimer, including 5,6-domain swapped dimers which have been proposed as the active, high affinity form (here the dimer interface lies between helices 5 and 6). The calculations suggest that the domain swapped dimer is a high energy structure in both the apo dimer and in the presence of propranolol. In the presence of agonist the energy of the domain swapped dimer is significantly lowered. Analysis of the dimer structure suggests that the agonist-induced conformational change optimizes the helix-helix interactions at the 5-6 interface. An antagonist on the other hand has little effect on these interactions. These observations are consistent with the hypothesis that the agonist functions by shifting the equilibrium in favour of the domain swapped dimer. Indirect support for the domain swapping hypothesis was obtained from the correlated mutations amongst the external residues of the known beta2-adrenergic receptors. These occur mainly at the 5-6 interface at precisely the locations predicted by the simulations; site-directed mutagenesis data in support of a functional role for these lipid-facing correlated residues is presented. The article includes a review of the experimental evidence for G-protein coupled receptor dimerization. Many other aspects of G-protein coupled receptor activation are discussed in terms of this domain swapping hypothesis

Amino Acid Sequence↗
PubMed1992

Relationship between chemical properties and biological properties of pyridoxalated hemoglobin-polyoxyethylene.

Pyridoxalated hemoglobin-polyoxyethylene (PHP) is a conjugate of human hemoglobin with alpha-carboxymethyl, omega-carboxymethoxypolyoxyethylene(POE). This conjugate is selected as an oxygen carrier for blood substitute because it can survive for a long time in the circulation and also it can transport the same amount of oxygen as red cell. Optimization of PHP has been done by changing the degree of the modification and reaction procedures in order to adjust viscosity and colloid osmotic pressure to physiological values. The oxygen carrying capacity was physically evaluated by oxygen equilibrium curves and biologically by an ATP content in perfused isolated liver. Structural relationship of PHP to the binding properties to haptoglobin was studied and the effect of the POE modification on the binding properties was observed when the number of POE per one hemoglobin molecule is over six. Based on the comparative study of solubility of met-PHP and met-SFH, the POE modification was suggested to reduce the toxicity of hemoglobin against organs. Finally physical properties of PHP at low temperature was discussed in relation to organ preservation.

Animals↗
PubMedDate not supplied

Electrochemical studies of some quinolone antibiotics. Part I. Qualitative analysis on mercury and carbon electrodes.

Direct current polarography and cyclic voltammetry was used to study quinolone antibiotics: ciprofloxacin, enoxacin, norfloxacin, ofloxacin and pefloxacin on a mercury and carbon electrode. The dependence of limiting currents and half-wave potentials on the pH of the solution, mercury head, temperature, ionic strength of the solution, methyl cellulose concentration, scan rate and quinolone concentration was studied. The optimal parameters and background solutions have been chosen. It was concluded that on mercury electrode quinolones are reduced in two one-electron waves and the process of the reduction is accompanied by an acid-base equilibrium. An anodic peak observed on graphite electrode is probably caused by the oxidation of piperazine ring in the molecule.

Anti-Infective Agents↗
PubMed1997

Efficient strategies for genome scanning using maximum-likelihood affected-sib-pair analysis.

Detection of linkage with a systematic genome scan in nuclear families including an affected sibling pair is an important initial step on the path to cloning susceptibility genes for complex genetic disorders, and it is desirable to optimize the efficiency of such studies. The aim is to maximize power while simultaneously minimizing the total number of genotypings and probability of type I error. One approach to increase efficiency, which has been investigated by other workers, is grid tightening: a sample is initially typed using a coarse grid of markers, and promising results are followed up by use of a finer grid. Another approach, not previously considered in detail in the context of an affected-sib-pair genome scan for linkage, is sample splitting: a portion of the sample is typed in the screening stage, and promising results are followed up in the whole sample. In the current study, we have used computer simulation to investigate the relative efficiency of two-stage strategies involving combinations of both grid tightening and sample splitting and found that the optimal strategy incorporates both approaches. In general, typing half the sample of affected pairs with a coarse grid of markers in the screening stage is an efficient strategy under a variety of conditions. If Hardy-Weinberg equilibrium holds, it is most efficient not to type parents in the screening stage. If Hardy-Weinberg equilibrium does not hold (e.g., because of stratification) failure to type parents in the first stage increases the amount of genotyping required, although the overall probability of type I error is not greatly increased, provided the parents are used in the final analysis.

Gene Frequency↗
PubMed1999

[Free radicals and extracorporeal renal replacement therapy].

Free radicals (FR), highly reactive substances with an unpaired electron in the outer orbital attack lipids, proteins and nucleic acids and alter the structure and function of these macromolecules. Against the negative effects of FR during evolution various defense mechanisms developed described comprehensively as antioxidant defense. Under physiological conditions in the organism equilibrium is established between free radical production and antioxidant defense factors. Extracorporeal renal replacement mechanisms can interfere in a negative way with this equilibrium. They provoke the formation of FR and at the same time they weaken the antioxidant defense e.g. by elimination of substances with antioxidant properties. Impairement of the equilibrium between FR production and antioxidant mechanisms to the disadvantage of antioxidant defense in patients with chronic renal failure was proved and is described as oxidative stress. Oxidative stress threatens dialyzed patients with serious clinical complications e.g. accelerated atherosclerosis, amyloidosis, haemolysis and the development of a state of chronic inflammation. Reduction of oxidative stress can be achieved by reducing FR production by using biocompatible dialyzation membranes, proper correction of acid-base disorders, by preventing an iron overload of the organism. The second approach is to foster the antioxidant defense by supplementation with antioxidants. Final recommendations as regards selection of the optimal dialyzation membrane, type of extracorporeal renal replacement and the amount and composition of antioxidant supplements have not yet been established and the problem is the subject of intense research.

Acid-Base Equilibrium↗
PubMed2005

Optimization of nonlinear optical properties by substituent position, geometry and symmetry of the molecule: An ab initio study.

Static polarizability and first- and second-order hyperpolarizability tensors are computed at the correlated level for a series of para-nitroaniline derivatives. The importance of including electron correlation effects in the determination of equilibrium structure and the molecular properties is investigated. A qualitative description of the substitution effects, planarity, and symmetric effect of the molecule on the molecular susceptibility is discussed.

Journal Article↗
PubMed1998

Thiol-disulfide redox buffers maintain a structure of immunoglobulin A that is essential for optimal in vitro binding to secretory component.

We have shown that human secretory component (SC) binds in vitro to different samples of human and murine dimeric immunoglobulin A (IgA). The binding ratio in the IgA/SC complex is 1:1. IgA which is stably bound to SC is separated from unreacted IgA by anion exchange chromatography. A part of IgA/SC complexes formed in vitro is unstable to this elution; the proportion varies between different samples of IgA; it increases following prolonged incubation of IgA at 37 degrees C. Incubation of IgA with glutathione/glutathione disulfide (GSH/GSSG) redox buffers increases the proportion able to form a stable complex with SC to approximately 90%. The presence of bound SC is not essential for this process but does allow it to occur at a lower GSH/GSSG concentration. The stable IgA/SC complex consists of a structure with a disulfide bond between IgA and SC apparently in equilibrium with a structure in which this bond is absent. The proportion bound covalently is similar for different samples of IgA and is insensitive to incubation with GSH/GSSG. It is significantly greater for secretory IgA (sIgA) and for IgA and SC incubated together with a starting mixture of cysteine/cystine. Monoclonal, antigen-specific IgA, all of which is optimally bound to SC in essentially the same way as in native sIgA, can be isolated in high yield. Our results support a mechanism for optimal binding of IgA to SC, that can occur both in vitro and in vivo, in which a thiol disulfide interchange occurs between a free IgA thiol and a sensitive SC disulfide following the initial non-covalent interaction.

Anion Exchange Resins↗
PubMed2004

Optimal composition of the dialysate, with emphasis on its influence on blood pressure.

UNLABELLED: Introduction. From the beginning of the dialysis era, the most appropriate composition of the dialysate has been one of the central topics in the delivery of dialysis treatment. METHODS: A discussion is employed to achieve a consensus on key points relating to the composition of the dialysate, focusing on the relationships with blood pressure behaviour. RESULTS: Sodium balance is the cornerstone of intra-dialysis cardiovascular stability and good inter-dialysis blood pressure control. Hypernatric dialysis carries the risk of positive sodium balance, with the consequent possibility of the worsening sense of thirst and hypertension. Conversely, hyponatric dialysis may lead to negative sodium balance, with the possibility of intra-dialysis cardiovascular instability and 'disequilibrium' symptoms including fatigue, muscle cramps and headache. The goal is to remove with dialysis the exact amount of sodium that has accumulated in the inter-dialysis interval. The conductivity kinetic model is applicable on-line at each dialysis session and has been proved to be able to improve intra-dialytic cardiovascular stability in hypotension-prone patients. Therefore, it should be regarded as a promising tool to be implemented in everyday clinical practice. Serum potassium concentration and variations during dialysis treatment certainly play a role in the genesis of cardiac arrhythmia. Potassium profiling, with a constant gradient between plasma and dialysate, should be implemented in clinical practice to minimize the arrhythmogenic potential of dialysis. Calcium plays a role both in myocardial contractility and in peripheral vascular resistance. Therefore, an increase in dialysate calcium concentration may be useful in cardiac compromised hypotension-prone patients. Acid-buffering by means of base supplementation is one of the major roles of dialysis. Bicarbonate concentration in the dialysate should be personalized in order to reach a midweek pre-dialysis serum bicarbonate concentration of 22 mmol/l. The role of convective dialysis techniques in cardiovascular stability is still under debate. It has been demonstrated that dialysate temperature and sodium balance play a role and this should be taken into account. Whether removal of vasoactive, middle-sized compounds by convection plays an independent role in improving cardiovascular stability is still uncertain. CONCLUSIONS: The prescription of dialysis fluid is moving from a pre-fixed, standard dialysate solution to individualization of electrolyte and buffer composition, not only during the dialysis session, but also within the same session (profiling) in order to provide patients with an optimal blood purification coupled with a high degree of tolerability.

Acid-Base Equilibrium↗
PubMed2006

Optimized heart failure therapy and complete anemia correction on left-ventricular hypertrophy in nondiabetic and diabetic patients undergoing hemodialysis.

BACKGROUND: According to new guidelines, diabetes mellitus per se can be considered as stage I chronic heart failure (CHF). Available evidence suggests that patients suffering from both diabetes mellitus and renal insufficiency have disproportionately high rates of left-ventricular hypertrophy (LVH). METHODS: Optimized heart failure therapy, including beta-blockers, ACE-inhibitors and AT II-type-1-receptor-blockers, was prescribed in combination with complete anemia correction using epoetin beta (target hemoglobin: 13.5 g/dl for women; 14.5 g/dl for men) to 230 patients (55% male) with ambulatory hemodialysis, including 60 patients (52% male) with diabetes. Echocardiographic follow-up examinations were performed over a mean period of 4.4 +/- 1.2 years. RESULTS: Mean hemoglobin levels at the study end significantly increased to target levels in the entire study population and in patients with diabetes (both p < 0.001). Compared with baseline, significant improvements were seen in hemodialysis patients - both without and with diabetes - in left-ventricular mass index (-28.8 g/m2 [p < 0.001] and 29.0 g/m2 [p < 0.005], respectively), left-ventricular ejection fraction (+7.0% [p < 0.001] and +8.3% [p < 0.01], respectively) and in NYHA class (-0.84 [p < 0.01] and -1.12 [p < 0.01], respectively). Similar to the results in the overall population, a highly significant reduction in LVH (p < 0.005) and significant improvements in LVEF (p < 0.01) and NYHA class (p < 0.01) were seen in the high-risk subgroup of diabetic patients. CONCLUSIONS: Patients undergoing hemodialysis, with or without concomitant diabetes, benefit considerably from optimized, multifactorial heart failure therapy combined with complete anemia correction.

Acid-Base Equilibrium↗
PubMed2001

Use of solid-liquid distribution coefficients to determine retention properties of Porapak-Q resins. Determination of optimal conditions to isolate alkyl-methoxypyrazines and beta-damascenone from wine.

The solid-liquid distribution coefficients of different analytes--all of which are important aroma compounds--between hydroalcoholic solutions or wines and different sorbents have been determined by measuring the amount of analyte removed by a given mass of sorbent in equilibrium with a given volume of standard solution. These data have shown that the best extraction conditions for non-polar compounds from wine are the use of Porapak-Q resins and 6% (v/v) alcoholic solutions. Phase ratio, hold-up volumes and number of plates for Porapak-Q beds have been measured in different experiments. With all these data it has been possible to calculate breakthrough volumes in good agreement with experimental results. The Lövkvist-Jönsson model is more appropriate for estimating breakthrough volumes of a 2-cm Porapak-Q bed. The model estimates that a 5-cm bed is needed to achieve a quantitative recovery of 3-alkyl-2-methoxypyrazines and beta-damascenone from 500 ml of wine (diluted to 1000 ml with water). Experimental results confirm the predictions of the model and show that in a single isolation step detection limits below 10 ng/l can be reached for these compounds using GC-MS detection.

Chromatography, Gas↗
PubMedDate not supplied

The optimization of pencil beam widths for use in an electron pencil beam algorithm.

Pencil beam algorithms for the calculation of electron beam dose distributions have come into widespread use. These algorithms, however, have generally exhibited difficulties in reproducing dose distributions for small field dimensions or, more specifically, for those conditions in which lateral scatter equilibrium does not exist. The work described here has determined that this difficulty can arise from the manner in which the width of the pencil beam is calculated. A unique approach for determining the pencil beam widths required to accurately reproduce small field dose distributions in a homogeneous phantom is described and compared with measurements and the results of other calculations. This method has also been extended to calculate electron beam dose distributions in heterogeneous media and the results of this work are presented. Suggestions for further improvements are discussed.

Algorithms↗
PubMed1996

Dynamic reaction design of enzymic biotransformations in organic media: equilibrium-controlled synthesis of antibiotics by penicillin G acylase.

Parameters relevant to the thermodynamically controlled synthesis of cephalothin utilizing highly active stabilized penicillin G acylase derivatives were studied. These included solubility/stability of substrates, enzyme derivative activity/stability, reaction course and synthetic yields. These parameters were altered by varying the pH, dimethylformamide concentration and temperature. Simultaneous optimization of the selected parameters could not be achieved with a single set of conditions. However, continuous adjustment of conditions throughout the reaction course allowed each parameter to be optimized (dynamic reaction design). This strategy works by optimizing those parameters that are critical to the overall reaction at a given point, whilst leaving others sub-optimal when their contribution to the total is minimal. This strategy has achieved a 90% transformation of antibiotic nucleus to cephalothin at a final concentration of 20 g/l, high enzyme and reactant stability, with a reaction period of 3 h (using 1 ml of derivative/40 ml of reaction solution).

Anti-Bacterial Agents↗
PubMed1989

Effect of sodium on [3H]ethylketocyclazocine binding to opioid receptors in frog brain membranes.

The specific binding of [3H]ethylketocyclazocine to frog brain membrane preparation was enhanced in the presence of sodium ions administered as NaCl, both at 0 degree C and at room temperature. The optimal NaCl concentration was 25 mM at 0 degree C and 50 mM at 24 degrees C. MgCl2 inhibited the [3H]ethylketocyclazocine binding. Two binding sites (high and low affinity) were established with [3H]ethylketocyclazocine as ligand by equilibrium binding studies. Addition of NaCl increased the Bmax of the low-affinity site more than that of the high-affinity site at both temperatures. Affinities were higher at 0 degree C than at 24 degrees C. The KD values were not significantly influenced by sodium ions. The dissimilarities between the rat and frog brain opioid receptors in [3H]ethylketocyclazocine binding are attributed to the different lipid composition of the two membranes.

Animals↗
PubMed2002

Structure of the (113)Cd(3)beta domains from Homarus americanus metallothionein-1: hydrogen bonding and solvent accessibility of sulfur atoms.

The three-dimensional structures of the isolated Cd(3)beta domains from Homarus americanus metallothionein have been determined by NMR methods in order to establish a set of beta-domain structures for comparative analysis. First, it was determined that the Cd-cysteine connectivities forming the Cd(3)S(9) metal center were identical to those observed for the beta(N) domain in the native holoprotein. Time- and temperature-dependence studies of the (113)Cd and (1)H 1D-NMR spectra indicated that the beta(N) domain undergoes slow conformational changes before reaching an equilibrium structure. In addition to structural information provided by the metal-to-cysteine connectivities, Phi, chi(1) and chi(2) angle constraints, three H(N...)S hydrogen bond interactions were also determined from a long-range optimized (1)H(N)-(113)Cd HMQC experiment. A simulated annealing protocol was applied to the distance and angle constraints obtained from the 2D-NMR experiments to calculate the three-dimensional structure of the synthetic Cd(3)beta(N) domain of lobster metallothionein. Structure-reactivity relationships are proposed for the reactions of Cd(3)beta domains with 5,5'-dithiobis(2-nitrobenzoate), based on comparisons of surface exposure of sulfur atoms of the lobster and rabbit Cd(3)beta domain structures. Finally, the surface exposure of the beta domains of lobster is compared with beta domains from mammalian metallothioneins.

Animals↗