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[Principles of conservative therapy of peripheral and central disorders of equilibrium].

Disturbance of equilibrium is a vestibular induced disturbance of orientation in space that is perceived subjectively as vertigo. Change of behaviour and specific medication is the optimal causal therapy, but symptomatic therapy is preferred in practice, using drugs that suppress different input activities or the activity of central vestibular structures. In this way a disordered flow of information is eliminated and the equilibrium is restored.

Brain↗

Growth of hygroscopic aerosols in a model of bronchial airways.

Experiments have been performed on the "breathing" of micron-size hygroscopic aerosols in and out of a four-generation model of the bronchial tree. Comparison of the experimental results on aerosol growth in the model with the classical theory for dilute aqueous solutions of nonpolar salts shows a) that the theory is applicable to conditions in the airways, b) that to a high degree of approximation the process represents deposition followed by growth, and c) that there is a significant amount of trapping of particles near their equilibrium size in the deeper model tubes. These experiments are the first to verify that the classical particle growth theory is applicable to the particle sizes and environmental conditions present in the human airways during hygroscopic aerosol therapy. This theory will be useful in designing an optimal hygroscopic aerosol delivery system, but several questions including the method of generation and the effect of drug solutions on particle equilibriums remain to be answered.

Aerosols↗

Equilibrium of phosphointermediates of sodium and potassium ion transport adenosine triphosphatase: action of sodium ion and Hofmeister effect.

Sodium and potassium ion transport adenosine triphosphatase accepts and donates a phosphate group in the course of its reaction sequence. The phosphorylated enzyme has two principal reactive states, E1P and E2P. E1P is formed reversibly from ATP in the presence of Na+ and is precursor to E2P, which equilibrates with P(i) in the presence of K+. We studied equilibrium between these states at 4 degrees C and the effect of Na+ on it. To optimize the reaction system we used a Hofmeister effect, replacing the usual anion, chloride, with a chaotropic anion, usually nitrate. We phosphorylated enzyme from canine kidney with [32P]ATP. We estimated interconversion rate constants for the reaction E1P <--> E2P and their ratio. To estimate rate constants we terminated phosphorylation and observed decay kinetics. We observed E1P or E2P selectively by adding K+ or ADP respectively. K+ dephosphorylates E2P leaving E1P as observable species; ADP dephosphorylates E1P leaving E2P as observable species. We fitted a 2-pool model comprising two reactive species or a twin 2-pool model, comprising a pair of independent 2-pool models, to the data and obtained interconversion and hydrolysis rate constants for each state. Replacing Na+ with Tris+ or lysine+ did not change the ratio of interconversion rate constants between E1P and E2P. Thus Na+ binds about equally strongly to E1P and E2P. This conclusion is consistent with a model of Pedemonte (1988. J. Theor. Biol. 134:165-182.). We found that Na+ affected another equilibrium, that of transphosphorylation between ATP x dephosphoenzyme and ADP x E1P. We used the reactions and model of Pickart and Jencks (1982. J. Biol. Chem. 257:5319-5322.) to generate and fit data. Decreasing the concentration of Na+ 10-fold shifted the equilibrium constant 10-fold favoring ADP x E1P over ATP x dephosphoenzyme. Thus Na+ can dissociate from E1P x Na3. Furthermore, we found two characteristics of Hofmeister effects on this enzyme.

Adenosine Diphosphate↗

Optimal thermal management for low birth weight infants nursed under high-powered radiant warmers.

Servocontrol of skin temperature for the critically ill premature neonate nursed on a radiant warmer bed has been assumed to be analogous to skin temperature control for infants nursed in convection-warmed incubators. There are significant differences between these two warming techniques, and no definitive data exist to aid the clinical specialist in governing radiant warmer control. Eighteen low birth weight premature infants less than 2 weeks of age were studied under powerful overhead radiant warmers to determine the optimal skin temperature for servocontrol of radiant heater output. Anterior abdominal wall temperature was servocontrolled at 35.5 degrees, 36.5 degrees, and 37.5 degrees C in a randomized fashion for three periods of 90 minutes each after thermal equilibrium was established. Oxygen consumption was measured during the entire 90-min sample period at each temperature by a computerized metabolic apparatus to determine the optimal thermal neutral control temperature defined as minimal oxygen consumption with normal body temperature. Skin, deep rectal, and environmental temperature measurements, as well as behavior assessments, were made concurrently. Oxygen consumption was significantly elevated at 35.5 degrees C (8.62 +/- 0.73 mL/kg/min, mean +/- SEM) compared with 36.5 degrees C (7.30 +/- 0.55 mL/kg/min). Changing servocontrol temperature to 37.5 degrees C produced no further significant decrease in oxygen consumption (7.41 +/- 0.70 mL/kg/min), and nine infants manifested supranormal deep rectal temperatures (greater than 37.5 degrees C). Optimal abdominal skin temperature control at 36.5 degrees C (slightly warmer than previously reported but less than 37.5 degrees C) is recommended for premature neonates nursed on radiant warmer beds.(ABSTRACT TRUNCATED AT 250 WORDS)

Beds↗

Continuous volume infusion improves circulatory stability in anesthesized rats.

'Optimized' management (OM) was provided to chloralose-anesthetized rats for 12 h by combining continuous infusion (7 ml.kg-1). mechanical ventilation and strict control of acid-base equilibrium (n = 7). The chloralose-anesthetized rats managed conventionally (conventional management: CM, n = 9) received neither volume infusion, nor mechanical ventilation, nor correction of acid-base disturbances. All the OM rats completed the study while 6 out of 9 CM rats died before the end of the study period. Mean arterial pressure (MAP) remained at 100 mmHg for 12 h in the OM group. MAP stayed close to 70 mmHg in the CM group for 6 h and declined to very low levels thereafter (mean +/- S.E.M.: 46.0 +/- 3.9 mmHg at 12 h, P less than 10(-4) when compared to the other group). Central venous pressure and cardiac output remained close to baseline values for 12 h in the OM group. Acid-base equilibrium was preserved in the OM group in contrast to a severe metabolic acidosis in the CM group (pH = 7.14 +/- 0.03 at 12 h; P less than 10(-4). Such as 'optimized' management involving mechanical ventilation with oxygen, continuous infusion and acid-base monitoring may be of value to maintain circulatory stability in anesthetized rodent preparations during long periods of time, as in neurophysiological experiments.

Anesthesia↗

Maximization of steady-state bacterial production in a chemostat with pH and substrate control.

This analytical study deals with the steady-state behavior and control of microbial growth in continuous cultures. A second order Haldane-Monod model of continuous cultures is used as a basis for study of the effects of the adjustment of pH by the addition of acidic (or basic) materials. The treatment of a hydrogen ion concentration, in addition to substrate and microbial concentrations as state variables, results in a third order system of equations describing the process. The analysis of the system in equilibrium yields several admissible steady states, that is, steady states which satisfy all constraints. An optimal control problem is formulated and subsequently solved to maximize steady-state microbial production.

Bacteria↗

The presence of angiotensin II receptors in elasmobranchs.

The presence of specific Ang II receptors in membrane fractions was investigated using 125I-labeled homologous Ang II ([Asn1, Pro3, Ile5]Ang II; df Ang II) in Triakis scyllia. Specific binding sites occurred in a variety of tissues, with highest binding in interrenal tissue (17.11 +/- 2.45 fmol Ang II/mg protein) and gill (6.26 +/- 0. 69 fmol Ang II/mg protein) and possible Ang II receptors in rectal gland and other tissues. 125I-[Asn1, Pro3, Ile5]Ang II (10(-10)M) binding to branchial cell membrane fraction (25 microg protein) in 5 mM MgCl2, 125 mM NaCl, 50 mM Tris-HCl, 0.2% bovine serum albumin at 28 degrees (1) is rapid and saturable; (2) increases as a function of membrane concentration and time; and (3) optimally fits to a two-site (high-and low-affinity) model. The equilibrium dissociation constant (0.11 +/- 0.01 nM) and binding site concentration (35.00 +/- 1.16 fmol/mg protein) are similar to those of mammalian and avian vascular Ang II receptors. Bound labeled ligand was not competitively displaced by dogfish Ang I, dogfish C-type natriuretic peptide, bradykinin, or the AT1 receptor antagonist, CV 11974. The AT2 receptor antagonist, CGP 42112, was much less potent at displacing the labeled ligand compared to the unlabeled ligand.

Angiotensin II↗

The maturase encoded by a group I intron from Aspergillus nidulans stabilizes RNA tertiary structure and promotes rapid splicing.

The AnCOB group I intron from Aspergillus nidulans self-splices, providing the Mg2+ concentration is >/= 15 mM. The splicing reaction is greatly stimulated by a maturase protein encoded within the intron itself. An initial structural and biochemical analysis of the splicing reaction has now been performed. The maturase bound rapidly to the precursor RNA (kon approximately 3 x 10(9) M(-1) min(-1)) and remained tightly bound (koff </= 0.04 min(-1)). The catalytic step of 5' splice-site cleavage occurred at a rate of up to 11 min(-1) under single turnover conditions. The maturase-assisted reaction of heat-denatured RNA proceeded at a rate of about 1 min(-1), arguing that there are early steps of folding that cannot be readily facilitated by the protein. pH analysis revealed a biphasic profile with a pKa of 7.0. The rate of the maturase-assisted reaction was independent of the Mg2+ concentration down to 3 mM. Self-splicing in optimal Mg2+ (>/= 150 mM) was tenfold slower, in part because of the existence of an equilibrium between folded and partially folded RNA. In contrast, the maturase very effectively stabilized tertiary structure in 5 mM Mg2+, a noticeable example being an interaction between the P8 helix and a GNRA sequence that constitutes the L2 terminal loop of the P2 helix. Formation of the 5' splice-site recognition helix was assisted by either the maturase or high concentrations of Mg2+. The maturase was required during splicing so it is not a true chaperone. However, RNase protection assays and kinetic studies suggest that the maturase recognizes and facilitates folding of an intron with limited tertiary structure and even incomplete secondary structure.

Aspergillus nidulans↗

Binding parameters of monoclonal antibodies reacting with ovarian carcinoma ascites cells.

Binding parameters were determined for four mouse monoclonal antibodies reacting with three antigens on the surface of fresh human ovarian carcinoma ascites cells, under nearly physiological conditions. The object of these experiments was to aid in the selection of the optimal monoclonal antibodies for intraperitoneal immunotherapy. The number of antigenic sites per cell, the effective equilibrium association constant (affinity) and the half-life for dissociation were: for Ab MH99, 1.2 x 10(6) sites/cell, (1.9-4.1) x 10(8) M-1, and 4 h; for Ab MX35, (3.2-4.1) x 10(5) sites/cell, (3.4-4.8) x 10(8) M-1, and greater than 10 h; and for Ab MW207, 1.3 x 10(5) sites/cell, (3.6-4.1) x 10(9) M-1, and 3.1 h, respectively. One of the antigens, MH99, is recognized by five different monoclonal antibodies, and competitive inhibition experiments demonstrated that two distinct determinants are present; this antigen is also recognized by the previously described Ab 17-1A. These binding data will aid the rational design of immunotherapy strategies.

Animals↗

On the stability of cognitive processes.

An empirical and mathematical model for self-organization is proposed, based on elemental properties, on unique interaction and on the combination of hierarchical elements. In the model, higher elements are stabilized by the 'cognitive' (strong) interaction of subelements, disregarding intermediate elements. This is called 'elementary reductionism' and is illustrated by the sequence quarks-elementary particles-atoms-molecules-cells-organisms- societies. Optimal dynamic interaction of nonidentical elements is called 'cognitive stability'. This is compared with thermodynamic equilibrium. The principal differences are outlined.

Actins↗

Plasma level monitoring of antiarrhythmic drugs.

It is widely accepted that the effects (both cardiac and extracardiac) of antiarrhythmic drugs are modulated by their concentration at some unidentified active site, and that the drug concentrations in the systemic circulation and at these active sites are in equilibrium. Thus, antiarrhythmic drug effects can be related directly to systemic plasma concentrations, and an optimal plasma concentration can be identified at which satisfactory arrhythmia suppression can be achieved in the absence of intolerable adverse effects. This optimal concentration is influenced by several factors that give rise to significant interpatient variability. These factors include serum protein binding, active metabolites, intrinsic responsiveness and myocardial accumulation. Although plasma concentration guidelines have been suggested for most antiarrhythmic drugs, they are generally not statistically derived and, with the exception of procainamide, are extrapolated from small patient samples. They generally represent the experience of an investigator or group of investigators treating a small homogeneous patient population. Interpretation of plasma concentrations of antiarrhythmic drugs also requires consideration of pharmacokinetic factors. Plasma drug levels are only useful when dosing history and timing of the blood sample, relative to drug administration, are considered. Despite several limitations, plasma concentration monitoring of antiarrhythmic drugs can be helpful if evaluated with an understanding of the pharmacokinetic properties of the drug being measured, the clinical status of the patient and an appreciation of the factors that may influence the relation between the measured level and resultant clinical response.

Anti-Arrhythmia Agents↗

Characterisation of the binding of [3H]FR115427, a novel non-competitive NMDA receptor antagonist, to rat brain membranes.

The binding of [3H]FR115427 ([3H](+)-1-methyl-1-phenyl-1,2,3,4- tetrahydroisoquinoline) to rat cortical synaptosomal membranes was investigated. Binding was optimal at pH 7.4-8.0, and temperature had little effect on specific binding. Binding reached equilibrium within 30 min at 25 degrees C, and was reversible in the presence of excess unlabelled FR115427. [3H]FR115427 bound to a single population of non-interacting sites with an affinity of 45.4 +/- 3.9 nM, and a binding site density of 9.12 +/- 0.52 pmol/mg protein. The affinities of other N-methyl-D-aspartate (NMDA) receptor channel blockers for [3H]FR115427 binding sites were consistent with binding to a similar site to that occupied by dizocilpine. Binding was potentiated by L-glutamate and glycine with EC50 values of around 80 nM. In the presence of L-glutamate (10 microM), specific binding was increased 4-fold, whilst addition of glycine (10 microM) increased specific binding 2-fold. FR115427 exhibited marked stereoselectivity; (+)-FR115427 has 100-fold higher affinity than (-)-FR115427. This ligand may therefore be useful for the pharmacological investigation of the NMDA receptor ion channel.

Animals↗

Synthesis of L-fucose 2-, 3-, and 4-sulphates.

Treatment of L-fucose with an excess pf pyridine-sulphur trioxide gave an equilibrium mixture of mono-, di-, and tri-sulphates. L-Fucose was sulphated under optimal conditions for monosulphate formation, and the monoester fraction was isolated by chromatography on DEAE-cellulose. The isomeric L-fucose 2-, 3-, and 4-sulphates (1-3) were separated on a DEAE-cellulose column by elution with borate buffer. The structures of 1-3 were established by electrophoresis, colour tests, periodate oxidation, and, for the 2-isomer, by comparison with a specimen of 1 that had been definitively synthesised via methyl 3,4-O-isopropylidene-alpha-L-fucopyranoside (6) and methyl alpha-L-fucopyranoside 2-(barium sulphate) (5). The latter was rapidly hydrolysed in hot, dilute acetic acid to 1 and methyl alpha-L-fucopyranoside (4).

Chemical Phenomena↗

Pore structure and adsorption performance of the activated carbons prepared from plum kernels.

According to iodine number, amount of methylene blue adsorption, the BET specific surface area, and the yield, the conditions for preparing activated carbons as adsorbents from plum kernels were optimized. The activation temperature and time tested were in the ranges 750-900 degrees C and 1-4 h, respectively. Adsorption isotherms of two commercial dyes and phenol from water on such activated carbons were measured at 30 degrees C. It was shown that the optimal activation temperature and time depended on the molar mass of the solutes, and all equilibrium isotherms could be fitted by the Langmuir equation. The experimental results indicated that the prepared activated carbons were economically promising for adsorption removal of dyes and phenol, in contrast to other commercial adsorbents.

Adsorption↗

Hand trajectory formation during whole body reaching movements in man.

End-effector trajectory formation was studied during a reaching movement using the whole body. The movements of various parts of the body were measured with the optoelectronic ELITE system. Wrist reaching movement paths showed noticeable curvatures. The analysis of various marker onset latencies revealed that the wrist was the last to move, always after the head, knee or trunk, suggesting a subordinate role of the focal component with respect to the primary role of the equilibrium component. These results suggest that reaching wrist movements are subjected to whole-body equilibrium constraints in addition to constraints placed upon end-effector kinematics or the dynamic optimization of upper-limb movements.

Adult↗

The design of a panel study under an alternating Poisson process assumption.

We discuss the design of a panel study for the estimation of the average durations in the two states of an alternating Poisson process. Two types of designs are examined. The first fixes the number of follow-up waves but permits the total length of follow-up to vary, and the second varies the number of follow-up waves with fixed length. Simple expressions for nearly optimal designs are presented, and we compare these with designs allowing for continuous observation. Both equilibrium and nonequilibrium cases are examined. An example is given using morbidity data to illustrate how these results can be applied.

Follow-Up Studies↗

Haemodiafiltration.

Using haemodiafiltration--a combination of haemodialysis and haemofiltration--an increased clearance rate for middle and small molecules can be obtained compared to the single technique alone. Low molecular weight substances are removed mainly by diffusion, and middle molecules predominantly by convection. Using currently available equipment the duration of therapy can thus be reduced by at least one-third, compared with haemodialysis, without deterioration in the patient's general condition. The withdrawal of large volumes of fluid is markedly better tolerated by the patient than with other short-time blood purification procedures. With the aid of haemodiafiltration both molecular groups can be diminished independently of each other according to individual demand, thereby leading to optimization of dialysis therapy.

Acid-Base Equilibrium↗

[Correlation of acid-base equilibrium and glycolysis during muscle activity].

Interdependence between acid-base equilibrium of blood and accumulation of lactate depending on the intensity of exertion during swimming and individual reaction to the exertion has been analyzed when examining high-qualification sportsmen. Prognostication and optimization criteria of acidosis prophylaxis are suggested.

Acid-Base Equilibrium↗