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Stability of meropenem and effect of 1 beta-methyl substitution on its stability in the presence of renal dehydropeptidase I.

The stability of meropenem in the presence of renal dehydropeptidase I (DHP-I) varied extremely with the animal source of the enzyme. Meropenem, compared with imipenem, was rather easily hydrolyzed by DHP-Is from mice, rabbits, and monkeys, while it showed a higher resistance to guinea pig and beagle dog DHP-Is. In addition, meropenem was four times more resistant than imipenem to human DHP-I. The 1 beta-methyl substituent on carbapenems, i.e., meropenem and 1 beta-methyl imipenem, made them considerably more resistant to mouse and swine DHP-Is than the 1-unsubstituted derivatives are.

Animals↗

[The stability of norepinephrine hydrogen tartrate, epinephrine hydrogen tartrate and isoprenaline sulfate. 29. The stability of drugs and preparations].

Stability testing of derivatives of brenzcatechine [norepinephrine hydrogentartrate (1), epinephrine hydrogentartrate (2), isoprenaline sulfate (3)] was carried out by stress investigation storing them at different temperatures. Substances of different charges which had been stored under normal conditions were analyzed. After a period of induction all three substances had been decomposed with a higher velocity. The order of kinetic process could not be determined. The storage life time was calculated by the aid of nonlinear regression. Time limit for storage of 5 years for 1 and 2 were confirmed. We suggest to extend it for 3 to 10 years.

Drug Stability↗

[The stability of hydrochlorothiazide and cyclopenthiazide in various dosage forms. 4. Stability of hydrochlorothiazide injection solutions II].

The hydrolytic decomposition of hydrochlorothiazide (1) in an optimized dispensing with polyethyleneglycol 400/ethanol as solvent led to an equilibrium in the isothermic short-term test as well as in the long-term stability test. Corresponding equilibrium concentrations were obtained for forward and back reaction. When comparing the precalculated equilibrium values with the long-term results the evaluation after Van't Hoff proved superior compared with an evaluation after the Arrhenius plot which is only applicable when the equilibrium concentrations are taken into consideration. By adding the decomposition product aminodisulfamide (2) the hydrolysis of 1 can be inhibited completely.

Cyclopenthiazide↗

[The stability of hydrochlorothiazide and cyclopenthiazide in various drug forms. 2. The stability of Disalunil tablets].

Checking-up the stability of hydrochlorothiazid tablets (Disalunil), chemical and especially pharmaceutical-technological analyses were forming part of the adequate test programme. The pharmaceutical and chemical properties of the Disalunil tablets will be regarded as sufficient ones at normal conditions of their storage. In case the tablets will be stored, however, in their original packing under conditions of an increased humidity or with additional water, the water sorption will result in prolonged disintegration rates as well as in a reduced radial breaking strength and dissolution rate. This significant depreciation of the drug cannot be recognized by chemical-analytical methods.

Cyclopenthiazide↗

[The effect of visible light on the stability of isoprenaline, epinephrine and levarterenol solutions in various containers. 86. Problems in the use of plastic containers for liquid preparations. 21. The stability of drugs and preparations].

The stability of solutions of phenylalkylamines of the benzcatechine type was investigated in containers of different structure under influence of diffuse day light, direct sun light and artificial visible light. Thereby a combined influence of different the decomposition increasing factors could be observed. The decompositions were slowest in containers of PE-ND with pigment additionals and were increased from PE-HD, PE-ND, colourless glas up to brown glas .

Drug Packaging↗

A molecular dynamics study of the structural stability of HIV-1 protease under physiological conditions: the role of Na+ ions in stabilizing the active site.

HIV-1 protease is most active under weakly acidic conditions (pH 3.5-6.5), when the catalytic Asp25 and Asp25' residues share 1 proton. At neutral pH, this proton is lost and the stability of the structure is reduced. Here we present an investigation of the effect of pH on the dynamics of HIV-1 protease using MD simulation techniques. MD simulations of the solvated HIV-1 protease with the Asp25/25' residues monoprotonated and deprotonated have been performed. In addition we investigated the effect of the inclusion of Na(+) and Cl(-) ions to mimic physiological salt conditions. The simulations of the monoprotonated form and deprotonated form including Na(+) show very similar behavior. In both cases the protein remained stable in the compact, "self-blocked" conformation in which the active site is blocked by the tips of the flaps. In the deprotonated system a Na(+) ion binds tightly to the catalytic dyad shielding the repulsion between the COO(-) groups. Ab initio calculations also suggest the geometry of the active site with the Na(+) bound closely resembles that of the monoprotonated case. In the simulations of the deprotonated form (without Na(+) ions), a water molecule bound between the Asp25 Asp25' side-chains. This disrupted the dimerization interface and eventually led to a fully open conformation.

Aspartic Acid↗

Influence of Temperature on Stability of Electrostatically Stabilized Alumina Suspensions.

Pure electrostatically stabilized aqueous alumina suspensions were prepared at various solid loadings in order to study the influence of temperature on the surface charge properties and rheology. Surface charge density at various temperatures was measured through potentiometric titration, and the analysis of the potentiometric data was accomplished using the constant capacitance surface model. Calculations of the pair-wise interaction potential between charged colloidal spheres dispersed in water were then carried out using conventional DLVO theory and a software package Stabil45, taking into account the temperature dependence of surface charge density and dielectric constant. The results showed that increasing temperature leads to a gradual diminution of alumina surface ionization, dielectric constant, and a total energy barrier for coagulation. The enhancement of the coagulation rate with increasing temperature leads to a gradual increase of both relative apparent viscosity and thixotropy. Copyright 2000 Academic Press.

Journal Article↗

Mechanisms of memory stabilization and de-stabilization.

Memories become stabilized through a time-dependent process that requires gene expression and is commonly known as consolidation. During this time, memories are labile and can be disrupted by a number of interfering events, including electroconvulsive shock, trauma and other learning or the transient effect of drugs such as protein synthesis inhibitors. Once consolidated, memories are insensitive to these disruptions. However, they can again become fragile if recalled or reactivated. Reactivation creates another time-dependent process, known as reconsolidation, during which the memory is restabilized. Here we discuss some of the questions currently debated in the field of memory consolidation and reconsolidation, the molecular and anatomical requirements for both processes and, finally, their functional relationship.

Animals↗

Posterolateral aspect and stability of the knee joint. II. Posterolateral instability and effect of isolated and combined posterolateral reconstruction on knee stability: a biomechanical study.

This study evaluated the correlation between the number of transected posterolateral structures (PLS) and the grade of posterolateral rotational instability, determined the effect of the popliteus muscle-tendon unit on the tibial rotation, and examined the effect of an isolated posterior cruciate ligament (PCL) and combined PCL-PLS reconstruction on knee stability. Sectioning the popliteofibular and lateral collateral ligaments both caused an increase in tibial external rotation. Cutting the PT resulted in a statistically highly significant excessive external rotation and externally shifted neutral position of the tibia over the full range of motion. Tensioning the popliteus muscle-tendon unit led to a statistically highly significant internally shifted neutral tibial rotation and a decreased internal and an increased external rotation without affecting the total rotational arcs. The isolated PCL reconstruction did not affect the external rotation, whereas the combined PCL-PLS reconstruction reset the knee to nearly physiological laxity patterns.

Adult↗

Stabilizing effect of the transferred conjoined tendon on shoulder stability.

The modified Boytchev procedure, i.e., rerouting of the coracoid process with its attached conjoined tendon (short head of biceps and coracobrachialis) deep to the subscapularis and reattachment to its anatomical location, has been advocated for recurrent anterior glenohumeral instability with controversial clinical outcomes. We aimed to investigate the dynamic contribution of the conjoined tendon in situ or transferred to the glenohumeral articulation in stable and unstable shoulders. Eight cadaveric shoulders were tested with the arm in 90 degrees abduction and 90 degrees external rotation. A constant 1.5 kg anterior translation force was applied to the proximal humerus, combined with 0, 1.5, 3.0 kg of load applied to the conjoined tendon sequentially. Anterior displacement of the humeral head relative to the scapula was recorded before and after an imitation Bankart lesion was created, and after treated with the modified Boytchev procedure for the Bankart lesion. Application of load to the conjoined tendon significantly reduced anterior displacement of the humeral head either with the capsule intact or with Bankart lesion simulated. The most significant decrease of the anterior displacement occurred when the conjoined tendon was transferred beneath the subscapularis. Our findings show that the conjoined tendon per se has a stabilizing effect on stable and unstable shoulders and therefore provide scientific support for the treatment of recurrent shoulder instability using the modified Boytchev procedure.

Adolescent↗

Fluorescence polarization studies on Escherichia coli membrane stability and its relation to the resistance of the cell to freeze-thawing. I. Membrane stability in cells of differing growth phase.

Physical properties of Escherichia coli membrane lipids in logarithmic- and stationary-phase cells were studied by measuring the fluorescence polarization change of cis- and trans-parinaric acid as a function of temperature. In aqueous dispersions of phospholipids extracted from cytoplasmic and outer membranes of cells of differing growth phase, a similar polarization increase was observed over the range from physiological temperature to below 0 degrees C, and nearly the same transition ratios were obtained in all samples. The cytoplasmic membrane of both of the growth-phase cells showed a higher polarization ratio above the transition temperatures, compared to that in the aqueous dispersion of phospholipids. The polarization ratios below the transition temperatures of these specimens were lower than the value obtained with the lipids, especially in the stationary-phase specimens. The outer membrane specimens showed a similar polarization change but the transition temperature ranges were considerably higher both in the logarithmic- and the stationary-phase specimens, compared to those in the cytoplasmic membrane specimens. Freeze-thawing of logarithmic-phase cells showed the emergence of activity of certain enzymes which are known to be located in the membranes. The stationary-phase cells did not suffer from any such deleterious effect and maintained a high level of cell viability in a similar treatment. These results indicate that in the stationary-phase cell membranes lipids are in a highly ordered state, and the lipid state causes a membrane stability which results in the high resistance of the cell to freeze-thawing.

Cell Membrane↗

Stability of phage T4 lysozymes. I. Native properties and thermal stability of wild type and two mutant lysozymes.

Two mutants of phage T4 lysozyme were prepared and characterized. One mutation substituted a tyrosine residue for tryptophan at position 138. The other substituted tyrosines at all three tryptophan positions of the wild type molecule (126, 138, 158). Comparative studies of the physical properties (absorption, fluorescence, circular dichroism) of the three enzymes were performed as a function of pH. Also, the proteins were reversibly melted as a function of pH. Since the unfolding reaction appeared to be a two-state process for all these proteins, the data were analyzed by the van 't Hoff procedure. The changes in stability and activity produced by substitution of Trp 138 were especially significant. The other substitutions were neutral. See the end of the paper for a summary of conclusions. In the appendix the appropriate thermodynamic relations are developed for a constant deltaCp transition.

Circular Dichroism↗

Is the hydrophobic effect stabilizing or destabilizing in proteins? The contribution of disulphide bonds to protein stability.

It has been recently concluded that the hydrophobic effect, hitherto regarded as a major driving force in the folding of proteins, destabilizes the folded state relative to the unfolded state. We summarize the properties of the hydrophobic effect obtained from solvent transfer experiments and show that the recent conclusion is an artifact of crosslinking in the unfolded state, caused by disulphide bonds, metals or cofactors. We show that, for the proteins in the data set, crosslinks surprisingly destabilize folded structures entropically, but stabilize them enthalpically to a greater extent. We also calculate non-polar surface areas of these unfolded proteins. These surface areas are decreased by crosslinks. The unfolded state of proteins lacking constraints, such as myoglobin, is well approximated by a mixture of residues containing alpha-helical and beta-sheet dihedral angles. Surface areas of unfolded proteins cannot be obtained by summing the surface areas of individual residues, since this ignores any unavoidable side-chain-side-chain interactions.

Disulfides↗

Stabilized bases using available undercuts for retention and stability.

When resilient tissue conditioner is adapted into the undercuts and bonded to acrylic resin base material, its resilience allows freedom to insert and remove the trial base and its softness provides protection from excessive abrasion of the cast. Available undercuts and intimate tissue contact provide greater stability and retention of the trial base.

Denture Bases↗

Stability of sagittal split osteotomies. A comparison of three stabilization techniques.

The objective of this study was to retrospectively evaluate stability of mandibular advancement after bilateral sagittal split osteotomies were performed. Three different fixation and immobilization protocols were examined. Thirty-three patients were evaluated with preoperative, immediate postoperative, and long-term (mean, 13 months) lateral cephalometric radiographs. The patients were divided into three groups: group 1 (n = 10) had nonrigid internal fixation and 6 weeks of maxillomandibular fixation, group 2 (n = 12) had rigid internal fixation and immediate postoperative function, and group 3 (n = 11) had rigid internal fixation with maxillomandibular fixation for a mean of 14 days. Group 3 had the least amount of sagittal and vertical relapse. Differences in sagittal relapse were statistically significant between groups 1 and 3. Group 2 demonstrated greater sagittal relapse than did group 3, although the result was not statistically significant. This study suggests that the use of rigid internal fixation with a period of maxillomandibular fixation appears to be more stable than nonrigid internal fixation with maxillomandibular fixation or rigid internal fixation without maxillomandibular fixation.

Adolescent↗

Within- and between-day stability of treadmill walking VO2 in children with hemiplegic cerebral palsy, stability of walking VO2 in children with CP.

Within- and between-day stability in locomotor energy use was quantified in 13 children with hemiplegic cerebral palsy (CP). During testing, subjects were familiarized with the laboratory environment (Session 1), performed three 5 min level treadmill walks (Trials 1-3) at 0.67 m*s(-1) (Session 2), and completed a single 5 min walk (Trial 4) at 0.67 m*s(-1) (Session 3). In Sessions 2 and 3, heart rate (HR) was assessed and expired air was collected and analyzed to determine VO2. Data analyses revealed no significant difference (P > 0.05) in either net VO2 (ml kg(-1)*min(-1)) or EEI(HR) (b*m(-1)) across the three trials performed in Session 2 and between average measures of net VO2 and EEI(HR) quantified in Session 2 and those obtained in Session 3. Mean within-day coefficient of variation (CV) values for net VO2 and EEI(HR) were 8.6% +/- 8.5% and 13.9% +/- 7.8%, respectively. Analysis of between-day variability and energy expenditure revealed a between-day CV value of 13.1% for net VO2 and 24.0% for EEI(HR). In addition, significant inverse relationships between Gross Motor Function Measure (GMFM) scores and within- (r = -0.61) and between-day (r = -0.58) CV values for net VO2 were detected. Viewed in concert, these data suggest that fairly stable within- and between-day measures of locomotor energy expenditure during level treadmill walking can be achieved in subjects with hemiplegic CP if testing is preceded by a short period of treadmill accommodation. However, children with greater motor dysfunction may require an extended period of treadmill accommodation to reduce trial-to-trial variability in walking energy use.

Adolescent↗

Within- and between-day stability of treadmill walking VO2 in children with hemiplegic cerebral palsy. Stability of walking VO2 in children with CP.

Within- and between-day stability in locomotor energy use was quantified in 13 children with hemiplegic CP. During testing, subjects were familiarized with the laboratory environment (Session 1), performed three 5-min level treadmill walks (Trials 1, 2, and 3) at 0.67 m x s-1 (Session 2), and completed a single 5-min walk (Trial 4) at 0.67 m x s-1 (Session 3). In Sessions 2 and 3, HR was assessed and expired air was collected and analyzed to determine VO2. Data analyses revealed no significant difference (P > 0.05) in either net VO2 (ml x kg-1 x min-1) or EEIHR (b x m-1) across the three trials performed in Session 2 and between average measures of net VO2 and EEIHR quantified in Session 2 and those obtained in Session 3. Mean within-day coefficient of variation (CV) values for net VO2 and EEIHR were 8.6% +/- 8.5% and 13.9% +/- 7.8%, respectively. Analysis of between-day variability and energy expenditure revealed a between-day CV value of 13.1% for net VO2 and 24.0% for EEIHR. In addition, significant inverse relationships between GMFM scores and within-day (r = -0.61) and between-day (r = -0.58) CV values for net VO2 were detected. Viewed in concert, these data suggest that fairly stable within- and between-day measures of locomotor energy expenditure during level treadmill walking can be achieved in subjects with hemiplegic CP if testing is preceded by a short period of treadmill accommodation. However, children with greater motor dysfunction may require an extended period of treadmill accommodation to reduce trial-to-trial variability in walking energy use.

Adolescent↗