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Biomedical subjects

B Gavish

Publications and source records attributed to B Gavish.

At least 19 recordsLinked to original sources
PubMed2001

Device-guided breathing exercises reduce blood pressure: ambulatory and home measurements.

Slow breathing practiced routinely using an interactive device has demonstrated a sustained reduction in high blood pressure (BP). We reevaluated the BP response of hypertensives (n = 13) to this daily treatment for 8 weeks using 24-h ambulatory, home, and office BP measurements. A clinically significant BP reduction of similar magnitude was observed in all BP monitoring modalities during the daytime. Greater BP reductions were found for older patients and higher baseline BP. The results provide additional support for the efficacy of the device as an adjunctive lifestyle modification for treating hypertension.

Adult↗
PubMed2001

Breathing-control lowers blood pressure.

We hypothesise that routinely applied short sessions of slow and regular breathing can lower blood pressure (BP). Using a new technology BIM (Breathe with Interactive Music), hypertensive patients were guided towards slow and regular breathing. The present study evaluates the efficacy of the BIM in lowering BP. We studied 33 patients (23M/10F), aged 25-75 years, with uncontrolled BP. Patients were randomised into either active treatment with the BIM (n = 18) or a control treatment with a Walkman (n = 15). Treatment at home included either musically-guided breathing exercises with the BIM or listening to quiet music played by a Walkman for 10 min daily for 8 weeks. BP and heart rate were measured both at the clinic and at home with an Omron IC BP monitor. Clinic BP levels were measured at baseline, and after 4 and 8 weeks of treatment. Home BP measurements were taken daily, morning and evening, throughout the study. The two groups were matched by initial BP, age, gender, body mass index and medication status. The BP change at the clinic was -7.5/-4.0 mm Hg in the active treatment group, vs -2.9/-1.5 mm Hg in the control group (P = 0.001 for systolic BP). Analysis of home-measured data showed an average BP change of -5.0/-2.7 mm Hg in the active treatment group and -1.2/+0.9 mm Hg in the control group. Ten out of 18 (56%) were defined as responders in the active treatment group but only two out of 14 (14%) in the control group (P = 0.02). Thus, breathing exercise guided by the BIM device for 10 min daily is an effective non-pharmacological modality to reduce BP.

Adult↗
PubMed2001

Treating hypertension with a device that slows and regularises breathing: a randomised, double-blind controlled study.

OBJECTIVE: To examine the efficacy of a new device, which slows and regularises breathing, as a non-pharmacological treatment of hypertension and thus to evaluate the contribution of breathing modulation in the blood pressure (BP) reduction. DESIGN AND SETTING: Randomised, double-blind controlled study, carried out in three urban family practice clinics in Israel. PATIENTS: Sixty-five male and female hypertensives, either receiving antihypertensive drug therapy or unmedicated. Four patients dropped out at the beginning of the study. INTERVENTION: Self treatment at home, 10 minutes daily for 8 consecutive weeks, using either the device (n = 32), which guides the user towards slow and regular breathing using musical sound patterns, or a Walkman, with which patients listened to quiet music (n = 29). Medication was unchanged 2 months prior to and during the study period. MAIN OUTCOME MEASURES: Systolic BP, diastolic BP and mean arterial pressure (MAP) changes from baseline. RESULTS: BP reduction in the device group was significantly greater than a predetermined 'clinically meaningful threshold' of 10.0, 5.0 and 6.7 mm Hg for the systolic BP, diastolic BP and MAP respectively (P = 0.035, P = 0.0002 and P = 0.001). Treatment with the device reduced systolic BP, diastolic BP and MAP by 15.2, 10.0 and 11.7 mm Hg respectively, as compared to 11.3, 5.6 and 7.5 mm Hg (P = 0.14, P = 0.008, P = 0.03) with the Walkman. Six months after treatment had stopped, diastolic BP reduction in the device group remained greater than the 'threshold' (P < 0.02) and also greater than in the walkman group (P = 0.001). CONCLUSIONS: The device was found to be efficacious in reducing high BP during 2 months of self-treatment by patients at home. Breathing pattern modification appears to be an important component in this reduction.

Adult↗
PubMed1998

Reduction of protein volume and compressibility by macromolecular cosolvents: dependence on the cosolvent molecular weight.

The partial specific volume (V) and adiabatic compressibility (beta) of myoglobin have been shown to be reduced by small cosolvents such as glycerol (A. Priev, A. Almagor, S. Yedgar, B. Gavish, Biochemistry 35 (1996) 2061-2066). To elucidate the effect of the cosolvent size on these protein properties, in the present study we determined V and beta of myoglobin in solutions containing a homologous cosolvent series from sucrose to dextran--500 (M.W. 500,000). It was found that in addition to the expected effect of the cosolvent concentration, V and beta decrease with increasing cosolvent M.W. This suggests that structural properties of the cosolvent contribute to its effect on the protein interior.

Animals↗
PubMed1997

An integrated noninvasive system for monitoring the microcirculatory effects of vasoactive drugs: an experimental study.

BACKGROUND: No information is available on the effects of vasoactive drugs on the microcirculation and on the correlation between their effects on the capillary and the systemic circulation. PURPOSE: To characterize the effects of nitroglycerin (NTG), nitroprusside (NP), and metaraminol infusion on microcirculatory variables using a noninvasive monitoring system. METHODS: Increasing doses of NTG (5-40 microg/kg/min) and NP (5-20 microg/kg/min) were intravenously infused to eight rabbits. The microcirculatory parameters were monitored by a combined noninvasive system which included laser Doppler flowmetry (LDF), photoplethysmograph (PPG), and transcutaneous oxygen tension (tc-PO2). Mean blood pressure (MBP) was measured simultaneously. RESULTS: At maximal rate of NTG infusion, the values of LDF, PPG, tc-PO2, and MBP were 72.2 +/- 23.9, 234.7 +/- 165.6, 103.5 +/- 37.4, and 82.7 +/- 7.4% of baseline, respectively. Following NP infusion the LDF, PPG, tc-PO2, and MBP reached 70.8 +/- 24.1, 190.5 +/- 68.9, 70.0 +/- 14.7, and 75.6 +/- 14.6% of baseline, respectively. The tissue oxygenation was significantly reduced during NP infusion compared to NTG (P < 0.05). The values gradually returned to the baseline 10 min after termination of NP infusion, but not after NTG. After injection of 1 mg metaraminol there was a steep decline in LDF, PPG, and tc-PO2 parallel to a significant increase in MBP. When metaraminol was administered after injection of 0.1 mg phenoxybenzamine, these changes were abolished. CONCLUSIONS: This noninvasive system effectively monitors microcirculatory hemodynamic changes induced by vasoactive drugs. NTG and NP cause similar changes in the systemic and microcirculatory bed, with the exception of peripheral oxygenation, which is reduced only during infusion of NP. The changes in the microcirculatory bed following metaraminol and phenoxybenzamine imply that their effects on the arterioles are mediated by adrenergic alpha-receptors.

Analysis of Variance↗
PubMed1996

Glycerol decreases the volume and compressibility of protein interior.

The addition of hydrogen-bonded cosolvents to aqueous solutions of proteins is known to modify both thermodynamic and dynamic properties of the proteins in a variety of ways. Previous studies suggest that glycerol reduces the free volume and compressibility of proteins. However, there is no directly measured evidence for that. We have measured the apparent specific volume (V) and adiabatic compressibility (K) of a number of proteins, sugars, and amino acids in water and in 30% glycerol at pH 7.4 and 30 degrees C. The values of V and K in water and their changes induced by glycerol were extrapolated to the limit of infinite solute size. The main results were the following: (a) glycerol decreases V and K of proteins, but increases it for amino acids; (b) the V and K values of the protein interior in water were found to be 0.784 +/- 0.026 mL/g and (12.8 +/- 2.5) x 10(-6) mL/g x atm, where the glycerol reduces these values by 8 and 32%, respectively; (c) the coefficient of adiabatic compressibility of the structural component of proteins affected by the glycerol is estimated to be (50 +/- 10) x 10(-6) atm(-1), which is comparable to that of water. We propose that the glycerol induces a release of the so-called "lubricant" water, which maintains conformational flexibility by keeping apart neighboring segments of the polypeptide chain. This is expected to lead to the collapsing of the voids containing the water as well as to increase intramolecular bonding, which explains the observed effect.

Amino Acids↗
PubMed1995

Viscosity dependence of O2 escape from respiratory proteins as a function of cosolvent molecular weight.

Laser photodissociation of respiratory proteins is followed by fast geminate recombination competing with escape of the oxygen molecule into the solvent. The escape rate from myoglobin or hemerythrin has been shown previously to exhibit a reciprocal power-law dependence on viscosity. We have reinvestigated oxygen escape from hemerythrin using a number of viscous cosolvents of varying molecular weight, from glycerol to dextrans up to 500 kDa. In isoviscous solutions, the strong viscosity dependence observed with small cosolvents is progressively reduced upon increasing the cosolvent's molecular weight and disappears at molecular weights greater than about 100 kDa. Thus, viscosity is not a suitable independent parameter to describe the data. The power of the viscosity dependence of the rate coefficient is shown here to be a function of the cosolvent's molecular weight, suggesting that local protein-solvent interactions rather than bulky viscosity are affecting protein dynamics.

Dextrans↗
PubMed1995

Noninvasive evaluation of microcirculatory hemodynamic changes during hemorrhage followed by saline or blood transfusion.

The purpose of the study was to examine the ability of a system combining laser Doppler flowmetry (LDF), photoplethysmograph (PPG), and transcutaneous oxygen tension (tc-PO2) to follow changes in the microcirculation during hemorrhage and following blood or saline return, and to test the hypothesis that such changes precede and might predict changes in the systemic blood pressure. Measurements were performed on the skin of anesthetized rabbits (n = 10) during mild (0-8%), moderate (9-24%), and severe (25-30% of blood volume) hemorrhage, and following complete volume restitution by blood or saline. We found the following: 1) hemorrhage caused typical changes in the LDF, PPG, and tc-PO2 signals that could be formulated by mathematical models, 2) these signals identified blood as being more efficient than saline for volume restitution following hemorrhage, and 3) microcirculatory changes precede and might predict systemic hemodynamic events.

Acute Disease↗
PubMed1994

Red blood cell aggregability is enhanced by physiological levels of hydrostatic pressure.

The effect of hydrostatic pressure of up to 15 bars on the aggregability of rat and human red blood cells (RBC), i.e., their capability to form aggregates, was studied using computerized image analysis. The aggregate size distribution was determined under ambient pressure, following application of hydrostatic pressure for various durations up to 2 h. It was found that RBC aggregability markedly increases, up to three-fold, as the pressure which had been applied was increased. Accordingly, higher shear stress is required for dispersing the aggregates of pressure-treated RBC than those of untreated cells. The median size of human RBC aggregates was about three times higher than that of rat RBC, and this ratio was maintained following pressure treatment. RBC aggregability is a major determinant in blood flow, especially in the microcirculation. Pressure at the levels used in this study occurs in physiological states such as hyperbaric treatment or diving. The enhanced aggregability induced by application of such pressure implies that blood flow in microvessels might be altered under conditions associated with elevated hydrostatic pressure.

Animals↗
PubMed1992

Viscous cosolvent effect on the ultrasonic absorption of bovine serum albumin.

Protein-ligand binding and enzyme activity have been shown to be regulated by solvent viscosity, induced by the addition of viscous cosolvents. This was indirectly interpreted as an effect on protein dynamics. However, viscous cosolvents might affect dynamic, e.g., viscosity, as well as thermodynamic properties of the solution, e.g., activity of solution components. This work was undertaken to examine the effect of viscous cosolvent on the structural dynamics of proteins and its correlation with dynamic and thermodynamic solution properties. For this purpose we studied the effect of viscous cosolvent on the specific ultrasonic absorption, delta mu, of bovine serum albumin, at pH = 7.0 and at 21 degrees C, and frequency range of 3-4 MHz. Ultrasonic absorption (UA) directly probes protein dynamics related to energy dissipation processes. It was found that the addition of sucrose, glycerol, or ethylene glycol increased the BSA delta mu. This increase correlates well with the solvent viscosity, but not with the cosolvent mass concentration, activity of the solvent components, dielectric constant, or the hydration of charged groups. On the grounds of these results and previously reported findings, as well as theoretical considerations, we propose the following mechanism for the solvent viscosity effect on the protein structural fluctuations, reflected in the UA: increased solvent viscosity alters the frequency spectrum of the polypeptide chain movements; attenuating the fast (small amplitude) movements, and enhancing the slow (large amplitude) ones. This modulates the interaction strength between the polypeptide and water species that "lubricates" the chain's movements, leading to larger protein-volume fluctuation and higher ultrasonic absorption. This study demonstrates that solvent viscosity is a regulator of protein structural fluctuations.

Absorption↗
PubMed1990

Solvent viscosity effects on protein dynamics studied by ultrasonic absorption.

Solvent viscosity is known to play an important role in the kinetics of biochemical reactions, and has been suggested to modulate the dynamic structure of proteins. The effect of viscous cosolvents, of various molecular sizes, on the apparent ultrasonic absorption of bovine serum albumin in solution, at 37 degrees, has been measured in attempt to investigate the following phenomena: 1) The predicted modulating effect of viscous cosolvents on the "internal friction" of proteins, and 2) Possible differences between the microscopic and macroscopic pictures of the solvent viscosity concerning the proposed effect. We have found that A) The absorption of ultrasound (3-17 MHz) by the protein increases with increasing the cosolvent concentration. B) That increase correlates with the solvent viscosity for small cosolvent molecules, but not with macromolecular cosolvents, and C) Dextran solutions with the same concentration by weight, reveal similar ultrasonic absorption, in spite of large differences in their viscosity. A possible explanation is discussed.

Absorption↗
PubMed1983

Adiabatic compressibility of globular proteins.

The adiabatic compressibility of several globular proteins has been measured by using an ultrasonic technique in the frequency range 0.5 to 10 MHz. The contributions to the measured compressibility from the protein matrix and from surface processes involving ionization of side chains and solvation effects are discussed. The internal protein compressibility is very low, indicating the existence of "dynamic domains" which are tentatively assigned to secondary structure elements.

Animals↗
PubMed1981

Modelling the unusual temperature dependence of atomic displacements in proteins by local nonharmonic potentials.

Recent x-ray studies of metmyoglobin at different temperatures [Frauenfelder, H. Petsko, G. A. & Tsernoglou, D. (1979) Nature (London) 280, 558-563] show that the dependence of the mean square displacements of individual atoms on the absolute temperature T can be described analytically by T mu, in which the parameter mu undergoes local variations in the range -2 to +20. This strong deviation from harmonic behavior mu = 1 is modelled here, in the classical limit, by local nonharmonic potentials, in which a particle spends part of its time in one or more weakly bound states (traps) and the rest of it as an almost free particle in a restricted volume (cavity). Analytic calculations of the mean square atomic displacement in such cavity--traps potentials for a simplified three-dimensional geometry yield the following results: A parametrically described T mu behavior characterizes a transition region in temperature below which the particle is "trapped" (solid-like) and above which the particle is "free" (liquid-like). The magnitude of mu increases with an increase in the ratio of cavity volume to trap volume. Mu greater than 0 type of behavior can be obtained by a single trap and mu less than 0 by two symmetric traps. A comparison is made between the predictions of the model and the experimental results, and the elucidation of the model parameters from x-ray data is discussed.

Mathematics↗
PubMed1981

pH dependence of the acetylcholine receptor channel: a species variation.

The effects of pH changes on the miniature endplate current (mepc) and on endplate current fluctuations (acetylcholine [ACh] noise) were examined at the neuromuscular junction in vitro in two species of frogs. In Rana pipiens the relationship between the decay time constant of the mepc (tau') and pH had a symmetrical bell shape; the value of tau' being largest at pH 7 and decreasing at more acid or more alkaline pH. In acid pH the mepc amplitude (A) decreased relative to its value at pH 7, and in alkaline pH A increased. In Rana ridibunda a narrower and asymmetric bell-shaped dependence of tau' on pH, having a maximum of pH 5.5, was found. The mepc amplitude was again reduced in acid pH but had a peak at pH 5.5. Also, its value at pH 9 was larger than at pH 7. These results were obtained with a number of different buffers and were not found to be sensitive to the nature of the buffer chosen. By performing ACh-noise analysis we found that in Rana pipiens at acid pH (5.5-5.0), the single channel conductance (gamma) and the single channel open time (tau) were significantly reduced relative to their value at pH 7. However, in Rana ridibunda at acid pH (5.4) gamma was unchanged and tau was markedly increased relative to their values at pH 7. The results can be explained quantitatively by electrostatic interaction between two fixed and titratable ionic groups and a mobile charge in the receptor molecule. The model fits the data for groups having pKs approximately 4.8 and approximately 9.8 for Rana pipiens and approximately 4.6 and approximately 6.3 for Rana ridibunda. The groups can be tentatively identified as amino acid residues; glutamic or aspartic and lysine or tyrosine for Rana pipiens; glutamic or aspartic and histidine for Rana ridibunda. The difference in the fitted values of the other model parameters for these two species can be attributed to differences in the spatial configuration of the charged groups.

Acetylcholine↗
PubMed1979

Offset rate of action of muscarinic antagonists depends on their structural flexibility.

Time course measurements of the action of muscarinic antagonists were performed in the spontaneously beating carp atrium. Several high affinity drugs, which embody the quinuclidine structure were examined. The structural flexibility of these molecules was reflected in the dissociation of the drugs from the muscarinic receptor. The dissociation of rigid drugs was very much prolonged as compared to flexible drugs of the same affinity.

Acetylcholine↗
PubMed1979

Viscosity-dependent structural fluctuations in enzyme catalysis.

The effect of viscosity on the rate of catalysis of carboxypeptidase A has been tested. By use of the tripeptide carbobenzoxy-l-alanyl-l-alanyl-l-alanine [Z(L-Ala)3] as substrate, it was shown that most of the effect on the hydrolysis rate caused by the presence of 30 or 40% methanol or glycerol in aqueous solution can be ascribed to a contribution of viscosity to the catalytic rate constant, kcat. Arrhenius plots of kcat in 30 and 40% glycerol or methanol are linear and almost parallel. When the rate constants are "corrected" for the viscosity of various media, the difference between the various Arrhenius plots is considerably reduced; it vanishes, within experimental error, when the effect of the dielectric constant of the solutions is taken into account as well. It is proposed that the viscosity of the medium can influence the rate-limiting step of the enzymic reaction, which is the rate of transitions over the energy barrier preceding product formation. According to the suggested mechanism, the enzyme--substrate complex can overcome this energy barrier by viscosity-dependent structural fluctuations. The quantitative agreement between the theory and the experimental results suggests that (a) due to the temperature dependence of the viscosity of the solution, the potential energy barrier of the reaction is about 5 kcal/mol lower than the observed activation energy and (b) information about the structural flexibility of the complex can be obtained by kinetic measurements.

Carboxypeptidases↗
PubMed1977

The role of geometry and elastic strains in dynamic states of proteins.

A theory is developed, where a linear macromolecule with geometrically constrained ends, elastically strained, exchanging energy with the solvent molecules through random collisions may provide a mechanism for the following specific functions in proteins: a) Induction of transient, oriented strains in substrates during transition between conformations. b) External variation of the rigidity and geometry of the active site. More generally, a macromolecule in solution possessing appropriate geometrical and elastic properties constitutes a machine, whose possible operations have common features with biological function such as passive transport, enzymatic catalysis and active transport. The theory suggests a quantitative law by which new information about the dynamical state of the protein molecule can be elucidated from the Arrhenius plot. It predicts a relationship between the rate of catalysis and the local viscosity of the solution.

Cytochrome c Group↗