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PubMed1998

Effective diffusion distance of nitric oxide in the microcirculation.

Despite its well-documented importance, the mechanism for nitric oxide (NO) transport in vivo is still unclear. In particular, the effect of hemoglobin-NO interaction and the range of NO action have not been characterized in the microcirculation, where blood flow is optimally regulated. Using a mathematical model and experimental data on NO production and degradation rates, we investigated factors that determine the effective diffusion distance of NO in the microcirculation. This distance is defined as the distance within which NO concentration is greater than the equilibrium dissociation constant (0.25 microM) of soluble guanylyl cyclase, the target enzyme for NO action. We found that the size of the vessel is an important factor in determining the effective diffusion distance of NO. In approximately 30- to 100-micron-ID microvessels the luminal NO concentrations and the abluminal effective diffusion distance are maximal. Furthermore, the model suggests that if the NO-erythrocyte reaction rate is as fast as the rate reported for the in vitro NO-hemoglobin reaction, the NO concentration in the vascular smooth muscle will be insufficient to stimulate smooth muscle guanylyl cyclase effectively. In addition, the existence of an erythrocyte-free layer near the vascular wall is important in determining the effective NO diffusion distance. These results suggest that 1) the range of NO action may exhibit significant spatial heterogeneity in vivo, depending on the size of the vessel and the local chemistry of NO degradation, 2) the NO binding/ reaction constant with hemoglobin in the red blood cell may be much smaller than that with free hemoglobin, and 3) the microcirculation is the optimal site for NO to exert its regulatory function. Because NO exhibits vasodilatory function and antiatherogenic activity, the high NO concentration and its long effective range in the microcirculation may serve as intrinsic factors to prevent the development of systemic hypertension and atherosclerotic pathology in microvessels.

Animals↗
PubMed1989

Seemingly paradoxical jumping in cataleptic haloperidol-treated rats is triggered by postural instability.

Paradoxically, animals exhibiting haloperidol-induced cataleptic immobility can be induced to leap vigorously, by pushing them forward from behind. It is shown here that such jumping can also be produced by placing them on a board and tilting it tail-end upward until about 50 degrees above horizontal. In both situations, jumps only occurred when the animal's hindlegs began to slip forward, as they lost their postural stability. As alternatives to jumping from the slope, rats turned to face upwards (negative geotaxis), or adopted a spread-eagled posture during head-first downward sliding, with the body and head flattened against the substrate. All 3 responses to the sloping board were present in some undrugged rats. Such rats, and those given low doses of haloperidol (0.5, 1.0 mg/kg), were more likely to turn upwards than to jump or slide. At high doses (7.5, 10.0 mg/kg), they were more likely to slide downward than to turn or jump. Jumping was most likely to occur at an intermediate dose (5 mg/kg), approximately 60 min after injection. We suggest that in the absence of haloperidol, and at low doses, locomotion is dominant over reflexes defending static equilibrium, and hence rats are more likely to turn upwards (which involves stepping). In contrast, at higher doses, locomotion is more fully suppressed, reducing the likelihood of turning. At very high doses of haloperidol and later in the action of the drug, muscle tonus appears to be weakened, reducing the likelihood of jumping. This possibility was supported by the finding that combined injection of the optimal dose of haloperidol and 2 mg/kg diazepam reduced the ability to cling vertically (suggesting weakness of muscle tone). In such rats, jumping from the sloping board was decreased, and active downward sliding was increased. Thus, different factors influence the occurrence of jumping at different doses of haloperidol. However, these are all active defensive responses to postural instability, and hence are similar to the other reflexes used by haloperidol-treated rats to defend against displacement from static stable equilibrium, such as standing immobile, bracing, clinging, and righting. Jumping in response to loss of stability on the sloping board also occasionally occurred in undrugged rats. Unlike jumps by haloperidol-treated rats, those by undrugged animals only occurred when they could be directed to a safe landing place. Thus, if the board faced the edge of the table, so that the jump would carry the animal into space over the edge, undrugged rats either did not jump or jumped off the side of the board onto the table.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2005

Conformational investigation of alpha,beta-dehydropeptides. N-acetyl-(E)-dehydrophenylalanine N'-methylamide: conformational properties from infrared and theoretical studies, part XIV.

N-Acetyl-(E)-dehydrophenylalanine N'-methylamide [Ac-(E)-DeltaPhe-NHMe], one of a few representative (E)-alpha,beta-dehydroamino acids, was studied by FTIR in dichloromethane and acetonitrile. To support spectroscopic interpretations and to gain some deeper insight into the Ac-(E)-DeltaPhe-NHMe molecule, the Ramachandran potential energy surface was calculated by the B3LYP/6-31G*//HF/3-21G method and the conformers localized were fully optimized at the B3LYP/6-31 + G** level. The spectra and calculations were compared with those of the related molecules Ac-DeltaAla-NHMe and Ac-(Z)-DeltaPhe-NHMe. The title compound assumes two conformational states in equilibrium in dichloromethane solution with a predominance of the extended conformer E. The Ac-(E)-DeltaPhe-NHMe spectrum is like that of Ac-DeltaAla-NHMe, particularly in the region of bands AI and AII, and unlike that of Ac-(Z)-DeltaPhe-NHMe. The positions of bands AI and II together with the nu(s)(N1--H1) band proves that the conformers E of both DeltaAla and (E)-DeltaPhe compounds are stabilized by the quite strong C5 hydrogen bonds N1--H1...O2. The same conclusion is drawn from the Ramachandran diagrams. The conformers E of both compounds are placed in the global minima and the gaps in energy order between them and the second conformer are large. The conformers E of DeltaAla and (E)-DeltaPhe, apart from the N1--H1...O2 hydrogen bond, show the Cbeta--H...O1 interaction, and Ac-(E)-DeltaPhe-NHMe displays the NH/pi interaction with the N2--H2 projecting in the first carbon atom of the phenyl ring. The C5 hydrogen bond is stronger in (E)-DeltaPhe than that in the DeltaAla compound. This is in agreement with interactions found in the calculated structures and can be explained by the influence of the phenyl ring in position (E). In acetonitrile, the molecule of Ac-(E)-DeltaPhe-NHMe loses its C5 hydrogen bond and becomes unfolded, whereas that of Ac-DeltaAla-NHMe does not vary practically. Adopting conformation E in a non-polar solvent seems to be a general feature of the (E)-DeltaXaa residues.

Hydrogen Bonding↗
PubMed1994

Mathematical analysis of coronary autoregulation and vascular reserve in closed-loop circulation.

The autoregulatory capacity of the coronary circulation has traditionally been studied in open-loop animal models where the coronary circulation was decoupled from the systemic circulation. In the closed-loop circulation, changes in arterial pressure alter coronary flow. Pressure variations can be caused by changes in cardiac contractility, preload, afterload, and heart rate. These changes also affect myocardial oxygen consumption. To maintain equilibrium between oxygen supply and consumption, coronary flow is altered by the autoregulation mechanism. Coronary resistance must change to produce the required change in coronary flow. The direction of change in coronary resistance is not directly predictable. Increased arterial pressure may result in either increased or decreased coronary resistance. To study the changes in coronary resistance in response to changes in arterial pressure that are produced by circulatory parameters, we used mathematical models. Coronary resistance was calculated to obtain equilibrium between ventricular oxygen consumption and supply for different values of contractility, preload, afterload, and heart rate. Maximum coronary resistance, indicating largest coronary vascular reserve and highest efficiency of arterial pressure generation, was defined as an optimal condition. The model predicted that the optimal value of cardiac contractility is its resting value. Minimizing end-diastolic volume and heart rate and maximizing peripheral resistance were shown to improve ventricular coronary vascular reserve. These observations suggest that afterload reduction therapy may not be beneficial for improving myocardial oxygen balance while venous vasodilatation and heart rate reduction result in greater coronary reserve.

Algorithms↗
PubMed1991

Modeling of immunosensors under nonequilibrium conditions. I. Mathematic modeling of performance characteristics.

Immunosensors for the detection of small analytes that use analyte-enzyme conjugates as signal generators require special attention if operated under nonequilibrium conditions. If the size of the analyte and the analyte-enzyme conjugate differ substantially, the two antigens do not diffuse at the same rate. This can cause time-dependent shifts in the sensitivity of competitive immunoassays. Therefore, immunosensors operating at short incubation times require precise timing that meets closely the specifications for which the sensors were calibrated. As an example, we have analyzed kinetic binding curves for the quantitative determination of progesterone with an immobilized monoclonal antibody and a conjugate between horseradish peroxidase and progesterone as signal generator. Mathematical paradigms have been developed to simulate the diffusion, antigen-antibody complex formation, and competitive binding processes in this analytical system. Dose-response curves obtained under nonequilibrium conditions can vary substantially from those obtained at equilibrium of antigen-antibody interaction. The degree of this variation depends on the performance characteristics of the major components of the immunosensor. The developed mathematical solutions reflect experimental results and can be used to model optimal conditions for immunosensors operating under nonequilibrium conditions. In this paper (Part I), we report on the mathematical modeling of the interaction between analyte, analyte-enzyme conjugate, and an immobilized antibody. In Part II (W. Schramm and S.-H. Paek (1991) Anal. Biochem. 196), we present experimental results and compare them with the theoretical models.

Antibodies↗
PubMed2006

Assembly of nucleic acid-lipid nanoparticles from aqueous-organic monophases.

Effective, reproducible, and scalable methods for DNA-lipid assembly are important for the success of non-viral vectors in in vivo gene therapy. We hypothesized DNA-lipid assembly would be optimal if started from a liquid monophase where both DNA and lipids separately form molecular or micellar solutions prior to mixing, without preexisting condensed lipid phases, thus allowing DNA-lipid assembly under conditions close to equilibrium. Previously, we found that mixing plasmid DNA, 1-palmitoyl-2-oleoyl-3-sn-phosphatidylcholine (POPC), cholesterol and a cationic lipid, 1, 2-dioleoyl-3-(trimethylammonio) propane (DOTAP) in 50% (v/v) aqueous ethanol spontaneously produced an optically transparent solution. Upon ethanol removal, DNA-lipid nanoparticles (Genospheres) were formed. For comparison with well-known technologies, different DNA-lipid particles were prepared by interaction of plasmid DNA and stable or ethanol-destabilized lipid vesicles by combining the components in water or 30% (v/v) aqueous ethanol, respectively. Among the three studied DNA-lipid assembly methods, only Genospheres combined the properties of small size (less than or around 100 nm), high incorporation of both lipid and DNA, high degree of DNA protection (dye accessibility 5-12%), a narrow distribution of particle density and when immuno-targeted, the highest transfection efficiency in HER2-overexpressing cells in vitro. We conclude that the Genosphere assembly methodology offers advantages for the development of effective, scalable and targetable non-viral gene delivery vectors.

Base Sequence↗
PubMed2001

Comparative ability of EMG, optimization, and hybrid modelling approaches to predict trunk muscle forces and lumbar spine loading during dynamic sagittal plane lifting.

OBJECTIVE: To compare the ability of three modelling approaches to resolve the muscle and joint forces in a lumbar spine model during dynamic sagittal plane lifting. DESIGN: Trunk muscle forces, spine compression, and coactivity predicted through double linear optimization, EMG-assisted, and EMG assisted by optimization approaches were compared.Background. The advantages of EMG-based approaches are known from static task analyses. Limited assessment has been made for dynamic lifting. METHODS: Eleven male subjects performed sagittal plane lifting-lowering at fixed cadence from 0 degrees to 45 degrees of trunk flexion with and without an external load of 12 kg. Three-dimensional kinematics and dynamics as well as surface EMG provided inputs to a 12 muscle lumbar spine model. RESULTS: Trunk muscle coactivity was different between the modelling approaches but spine compression was not. Both EMG-based approaches were sensitive to trunk muscle coactivity and imbalance in left-right muscle forces during sagittal plane lifting. Overall, the best correlations between predicted forces and EMG as well as between forces predicted by different modelling approaches were obtained with the EMG-based models. Only the EMG assisted by optimization approach simultaneously satisfied mechanical and physiological validity. CONCLUSIONS: Both EMG-based approaches demonstrated their potential to detect individual trunk muscle strategies. A more detailed trunk anatomy representation would improve the EMG-assisted approach and reduce the adjustment to muscle force gain through EMG assisted by optimization. RELEVANCE: Injury to the lumbar spine could command alternative strategies of motion to attenuate pain and damage. To understand these strategies, the ideal lumbar spine model should predict individual muscle force patterns and satisfy mechanical equilibrium.

Adult↗
PubMed2002

Enhanced brain targeting by synthesis of 3',5'-dioctanoyl-5-fluoro-2'-deoxyuridine and incorporation into solid lipid nanoparticles.

To overcome the limited access of the drug 5-fluoro-2'-deoxyuridine (FUdR) to the brain, 3',5'-dioctanoyl-5-fluoro-2'-deoxyuridine (DO-FUdR) was synthesized and incorporated into solid lipid nanoparticles (DO-FUdR-SLN). DO-FUdR-SLN were prepared by a thin-layer ultrasonication technique and a central composite design (CCD) was applied to optimize the formulation. The median particle size of DO-FUdR-SLN was 76 nm with drug loading of 29.02% and entrapment efficiency of 96.62%. The in vitro drug release was studied by a bulk-equilibrium reverse dialysis bag technique in phosphate-buffered saline (pH 7.4) containing 0.3% pancreatic enzyme at 37 degrees C. The concentrations of FUdR in various organs were determined by reversed-phase high-performance liquid chromatography after intravenous administration of DO-FUdR-SLN, DO-FUdR or FUdR. The brain area under the concentration-time curve of DO-FUdR-SLN and DO-FUdR were 10.97- and 5.32-fold higher than that of FUdR, respectively. These results indicated that DO-FUdR-SLN had a good brain targeting efficiency in vivo. SLN can improve the ability of the drug to penetrate through the blood-brain barrier and is a promising drug targeting system for the treatment of central nervous system disorders.

Animals↗
PubMed1997

Favourable native-like helical local interactions can accelerate protein folding.

BACKGROUND: Extensive studies of peptide conformation have provided reasonable knowledge of the rules determining helix stability. This knowledge can be used to stabilize proteins against chemical and thermal denaturation. This has been done in two proteins: the chemotactic protein from Escherichia coli, Che Y (a 129 aa alpha/beta parallel protein with five alpha-helices, which shows an accumulating intermediate during refolding) and the activation domain of human procarboxypeptidase A2, ADA2h (a 81 aa alpha + beta protein domain, with two alpha-helices, which follows a two-state mechanism). As the introduced stabilizing interactions are local in nature, the energy balance between the contribution of local and nonlocal interactions changes considerably. Recent theoretical analyses of protein folding using simplified models have indicated that optimization of folding speed requires this balance to be biased towards nonlocal interactions. To determine whether this is the case, we study here the folding kinetics of two ADA2h mutants in which alpha-helix 1 (mutant M1) or 2 (mutant M2) has been stabilized through local interactions, as well as the equilibrium and kinetic behaviour of a double mutant (DM) in which both helices have been stabilized. RESULTS: The stability of DM is considerably enhanced with respect to wild type (WI) and this mutant can be considered as a thermoresistant protein (Tm > 363 K). The thermodynamic parameters obtained by chemical denaturation (urea and GdnHCl) show that DM is approximately 2.6 kcal mol-1 more stable than WT. The effects on folding kinetics are different in each of the single mutants. M1 shows very little effect in refolding, while its unfolding is greatly decelerated with respect to WT. M2 shows, together with a deceleration in unfolding, a significant acceleration in refolding. As with equilibrium parameters, the kinetics of the double mutant can be explained by the simple addition of the effects found in each single mutant. Interestingly enough, the refolding slope mkf in mutants M2 and DM is smaller than in the wild-type and M1 mutant. CONCLUSIONS: Thermoresistance can be achieved, in some cases, by increasing favourable native local interactions. The balance between local and nonlocal interactions can be significantly changed in some proteins and still keep a cooperative unfolding transition similar to that of the wild type. The introduction of favourable local interactions by mutational redesign can also be used to increase the folding speed of certain proteins, showing that not all proteins in nature have been optimized for rapid folding, contrary to what has been theoretically indicated. This behaviour is probably also shared by other polypeptides with highly unstructured denatured states. All these phenomena have been shown experimentally in ADA2h by mutations that increase helix stability. However, the effects promoted for such an approach in proteins with residual structure and/or intermediates in the denatured ensemble could be different. This has been shown by experiments performed on CheY in which the cooperativity of the folding process was greatly affected.

Adaptor Proteins, Signal Transducing↗
PubMed1980

Properties of a purified nucleolar ribonuclease from Ehrlich ascites carcinoma cells.

A nucleolar ribonuclease specific for single-stranded ribonucleic acid (RNA) has been isolated and extensively purified from Ehrlich ascites carcinoma cells. The enzyme is optimally active at neutral pH and degrades RNA via a 2',3'-cyclic intermediate leaving 3'- or 2',3'-cyclic terminated oligonucleotides. The ribonuclease has an apparent molecular weight of 38 500 as judged by sedimentation equilibrium and is a basic protein having an isoelectric point greater than 9.0. The enzyme preferentially cleaves poly(C) over poly (U), poly(A), or poly(C).poly(I). Limit digestion products of poly(C) degratation are on the average tri-, tetra-, and pentanucleotides. In the partial digestion of yeast 5.8S rRNA, the nucleolar ribonuclease cleaves only CpA phosphodiester bonds. Spermidine, spermine, and histone I inhibit the activity of nucleolar ribonuclease. Antibodies directed toward pancreatic RNase do not cross-react with the Ehrlich nucleolar ribonuclease.

Animals↗
PubMedDate not supplied

Fine affinity discrimination by yeast surface display and flow cytometry.

Yeast surface display is a eucaryotic system for the directed evolution of protein binding and stability. For antibody affinity maturation, achievable single-pass enrichment factors are a critical variable. Both reliable recovery of rare clones (yield) and effective differentiation between clones of only slightly improved affinity (purity) are paramount. To validate yeast display's purification potential, trial sorting experiments were performed. The D1.3 (anti-hen egg lysozyme) single chain variable fragment antibody and a 2-fold higher affinity mutant (M3) were each displayed on the surface of Saccharomyces cerevisiae. M3-displaying cells were mixed into the D1.3-displaying cells at a ratio of 1:1000. Cells were fluorescently labeled according to antigen equilibrium binding and then sorted using a flow cytometer. Single-pass enrichment of M3-displaying cells was 125-fold (+/- 65-fold). This level of performance is achievable because of the precision and reproducibility of optimal labeling conditions. This work further demonstrates the capability of yeast display for very fine discrimination between mutant clones of similar affinity. Because large improvements in affinity typically result from combinations of small changes, this capability to identify subtle improvements is essential for rapid affinity maturation.

Animals↗
PubMed1996

Purification of the Chlorella HUP1 hexose-proton symporter to homogeneity and its reconstitution in vitro.

A prokaryotic biotin acceptor domain was fused to the carboxy terminal end of the Chlorella hexose-proton symporter. The plant symporter is biotinylated in vivo when expressed in Schizosaccharomyces pombe. The extended biotinylated transport protein is fully active, catalyzes accumulation of D-glucose analogs and restores growth of a glucose-uptake-deficient yeast strain. Crude membranes were solubilized with octyl-beta-D-glucoside in the presence of Escherichia coli L-alpha-phosphatidylethanolamine. Biotinylated symporter was purified to homogeneity by biotinavidin affinity chromatography. The symporter protein was reconstituted together with cytochrome-c oxidase prepared from beef heart mitochondria into proteo-liposomes. Cytochrome-c oxidase is a redox-driven H(+)-pump generating a proton motive force (inside negative and alkaline) while transferring electrons from cytochrome-c to oxygen; this energy is used by the symporter to accumulate D-glucose at least 30-fold. In the absence of the driving force the transport protein facilitates diffusion of D-glucose until the concentration equilibrium is reached. It was shown that maximal transport activity depends highly on the amount of co-reconstituted cytochrome-c oxidase and that the symporter possesses 10% of its in vivo turnover number under optimized in vitro transport conditions.

Amino Acid Sequence↗
PubMed1996

Randomized outcome trial of human milk fortification and developmental outcome in preterm infants.

Despite potential benefits, human milk may fail to meet preterm infants' nutrient requirements. We tested the hypothesis that fortified breast milk, fed alone or with preterm formula, would improve neurodevelopment and growth at 18-mo follow-up without adverse short-term clinical or biochemical consequences. Two hundred seventy-five preterm infants from two medical centers (birth weight < 1850 g; mean gestation 29.8 +/- 2.7 wk) whose mothers chose to provide breast milk were randomly assigned to receive for a mean of 39 d a multinutrient fortifier or control supplement containing phosphate and vitamins. Breast milk comprised 47.6% and 46.4% of enteral intake in fortified and control groups, respectively; preterm formula supplements were used when insufficient breast milk was available. Overall, there were no significant growth advantages with fortification; although, when breast milk exceeded 50% of intake, fortification promoted faster weight gain (an advantage of 1.6 g.kg-1.d-1; 95% CI: 0.1, 3.1; P < 0.05). Compared with control infants, the fortified group showed 1) higher plasma urea from week 2 (P = 0.04), 2) higher plasma calcium (mean 2.34 +/- 0.01 compared with 2.27 +/- 0.02 mmol/L; P = 0.003), 3) a greater rise in alkaline phosphatase by week 6 (P = 0.04), 4) more clinical infections (suspected plus proven; 43% compared with 31%, P = 0.04), 5) a nonsignificantly increased incidence of necrotizing enterocolitis (5.8% compared with 2.2%, P = 0.12), and 6) higher white cell and platelet counts. Developmental scores at 18 mo were slightly but not significantly higher in the fortified group. This study confirmed that breast milk fortifiers can improve short-term growth (when breast milk intakes are high); but beneficial effects on long-term development remained unproven. Future research is required to evaluate potential adverse consequences and explore more optimal fortification strategies.

Acid-Base Equilibrium↗
PubMed2003

Significance of affinity and cooperativity in oxygen binding to hemoglobin of horse fetal and maternal blood.

The physiological significance of the position and shape of the oxygen equilibrium curve (OEC) of horse hemoglobin (Hb) is considered from the viewpoint of oxygen (O2) transport efficiency and the effectiveness of the Bohr effect. In horse fetal and maternal bloods, their physiological O2 affinities are nearly optimized with respect to the effectiveness of the Bohr shift occurring at the O2 release site, when it is measured by the change in O2 saturation per unit change in P50. With relatively low cooperativity (n=2.69) of horse Hb under physiological conditions, the effectiveness of the Bohr shift for fetal blood at O2 uptake site and maternal blood at O2 release site is high. These facts imply that the position and the cooperativity of horse Hb OEC are optimized to receive maximal benefit from the double Bohr shift. Before exercise, the position of the OEC for adult mares is nearly optimized for the effectiveness of the Bohr shift occurring at the O2 release site, whereas, at maximal exercise, the position of the OEC tends to become advantageous for O2 transport efficiency.

2,3-Diphosphoglycerate↗
PubMed2005

Biosorption of cadmium by fungal biomass of Aspergillus niger.

OBJECTIVE: To investigate the removal of cadmium from aqueous solution by waste fungal biomass of Aspergillus niger, originated from citric acid fermentation industry. METHODS: Batch adsorption test was used to study the biosorption equilibrium and isotherm. The Cd2+ concentration was measured with atomic adsorption spectrophotometer (AAS) HITACHI 180-80. RESULTS: The biosorption achieved equilibrium within 30 min. The adsorption isotherm could be described by Freundlich adsorption model, and the constants K(F) and 1/n were determined to be 2.07 and 0.18, respectively, and the correlation efficiency was 0.97. The optimal pH for Cd adsorption was 6.0. The cadmium-laden biomass could be effectively regenerated using 0.1 N HCl. CONCLUSION: The waste biomass of Aspergillus niger, a by-product of fermentation industry, is a potential biosorbent for the removal of cadmium from aqueous solution.

Adsorption↗
PubMed1977

[Metabolism and action of intracellular magnesium (author's transl)].

The activity of Mg2+-activated enzymes shows a bell shaped pMg dependency, with a pMg optimum at 3. Intracellular Mg2+ concentrations, determined by different methods, are about 10(-3) mol/1. Thus Mg2+-dependent enzymes are optimally activated, or nearly so, with Mg2+. If the substrates of an enzyme form complexes with Mg2+ of different stabilities, and if free substrate and the substrate-Mg2+ complex react differently with the enzyme, the equilibrium will change with the concentration of Mg2+. When the extracellular concentration of Mg2+ is increased, Mg2+ becomes bound practically exclusively to the cell membrane. In Mg2+ deficiency, the intracellular concentrations of Na+, K+, Ca2+ and cycl. AMP are changed, and the rates of synthesis of DNA, RNA and protein are decreased.

Animals↗
PubMed1984

Protein requirements with very low calorie diets.

The goal of the dietary treatment of obesity is to reduce the patient's weight with minimum risk. This is accomplished by a dietary regimen which allows a preferential loss of body fat with a preservation of lean body mass. Total fasting leads to a loss of 150 grams of nitrogen in the first month alone. In a study by Hoffer et al. reported below, two levels of dietary protein were compared for their effects on nitrogen balance in 17 obese women on a low calorie (500 cal) weight reduction diet. After three weeks of adaptation to the diets, the group given 0.8 grams protein/kg were in -2 grams nitrogen balance while the group given 1.5 grams protein/kg were at zero nitrogen balance. It was concluded that protein intakes at the level of the recommended dietary allowance (0.8 g/kg) are not compatible with nitrogen equilibrium when the energy intake is severely restricted. While weight loss is the obvious goal for obese persons, a careful examination of the composition of the weight loss (protein, fat, water) is essential in defining the optimal dietary regimen.

Adult↗
PubMed1998

Effects of Optimal Antipredator Behavior of Prey on Predator-Prey Dynamics: The Role of Refuges.

The influence of optimal antipredator behavior of prey on predator-prey dynamics in a two-patch environment is studied. One patch represents an open habitat while the other is a refuge for prey. It is assumed that prey maximize their fitness measured by the instantaneous per capita growth rate. In each patch population dynamics is described by the Lotka-Volterra time continuous model. The refuge is characterized by its protectiveness which is inversely related to the predation risk for prey, and the dependence of population dynamics on protectiveness is studied. It is shown that adaptive behavior of prey changes qualitative properties of the underlying Lotka-Volterra model due to the appearance of a bounded attractor. Adaptive prey behavior does not lead to a stable equilibrium but to the reduction of population fluctuations. Dynamic consequences of a limited carrying capacity of the refuge are also considered. Low refuge carrying capacity leads to stability of predator-prey dynamics while stability is lost when the carrying capacity of the refuge is high. Lastly, it is shown that optimal antipredator behavior of prey leads to persistence and reduction of oscillations in population densities. Copyright 1998 Academic Press.

Journal Article↗