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At least 1,675 records · Page 93Linked to original sources
PubMed1998

Liquid chromatographic analysis in mouse, dog and human plasma; stability, absorption, metabolism and pharmacokinetics of the anti-HIV agent 2-chloro-5-(2-methyl-5,6-dihydro-1,4-oxathiin-3-yl carboxamido) isopropylbenzoate (NSC 615985, UC84).

NSC 615985 (UC 84) has demonstrated anti-HIV activity in the NCI-AIDS antiviral screen and was under consideration as an anti-AIDS drug. The compound was subsequently shown to be a non-nucleoside reverse transcriptase inhibitor (NNRTI). An HPLC method was developed for the analysis of NSC 615985 in mouse, dog and human plasma; and was used to study its stability in plasma and blood as well as its absorption and metabolism in mice. The method involved precipitation of plasma protein with three volumes of methanol followed by HPLC analysis of the supernatant. The HPLC analysis was carried out on a reversed-phase Nova-Pak C18 column with a mobile phase of KH2PO4 (0.01 M; pH 4.8)-acetonitrile (52:48, v/v) at a flow rate of 1 ml min-1 and quantification with a UV detector set at 259 nm. The lower limit of quantitation was 0.05 microgram ml-1 in 1 ml of dog or human plasma or 0.1 microgram ml-1 in 0.5 ml of mouse plasma. NSC 615985 was more stable in dog and human plasma than in mouse plasma, and was less stable in blood than in plasma of the three species investigated. Following bolus intravenous (i.v.) administration at 10 mg kg-1 to male CDF1 mice, NSC 615985 elimination followed biexponential kinetics with half-lives of 1 and 7 min, and was extensively metabolized. NSC 615985 was very poorly absorbed following oral (PO) administration as a suspension in water or in 20% lipid emulsion (Liposyn II). Following bolus subcutaneous (s.c.) administration of [14C]NSC 615985 at 10 mg kg-1, relatively low concentrations of the parent compound were observed in three of 36 mice. One metabolite was tentatively identified in plasma of both the i.v.- and s.c.-treated animals as the sulfoxide of the parent compound. No parent compound was detected in the urine of NSC 615985 dosed mice. At least seven metabolites were present in urine; one metabolite (constituting 8-14% of urinary radioactivity) was tentatively identified as the carboxylic acid resulting from the hydrolysis of the isopropyl group from the parent compound. In summary, NSC 615985 was poorly absorbed following oral administration and extensively metabolized and eliminated following i.v. or s.c. administration. This unfavorable pharmacokinetic profile of NSC 615985 as well as its pattern of activity against NNRTI-resistant strains of HIV-1 precluded its progression to clinical trial; however, other members of the general chemical class are currently being evaluated by the NCI.

Animals↗
PubMed1999

Contribution of hydrogen bonds to the conformational stability of human lysozyme: calorimetry and X-ray analysis of six Ser --> Ala mutants.

To further examine the contribution of hydrogen bonds to the conformational stability of the human lysozyme, six Ser to Ala mutants were constructed. The thermodynamic parameters for denaturation of these six Ser mutant proteins were investigated by differential scanning calorimetry (DSC), and the crystal structures were determined by X-ray analysis. The denaturation Gibbs energy (DeltaG) of the Ser mutant proteins was changed from 2.0 to -5.7 kJ/mol, compared to that of the wild-type protein. With an analysis in which some factors that affected the stability due to mutation were considered, the contribution of hydrogen bonds to the stability (Delta DeltaGHB) was extracted on the basis of the structures of the mutant proteins. The results showed that hydrogen bonds between protein atoms and between a protein atom and a water bound with the protein molecule favorably contribute to the protein stability. The net contribution of one intramolecular hydrogen bond to protein stability (DeltaGHB) was 8.9 +/- 2.6 kJ/mol on average. However, the contribution to the protein stability of hydrogen bonds between a protein atom and a bound water molecule was smaller than that for a bond between protein atoms.

Alanine↗
PubMed2000

Strategies used to stabilize the elbow joint challenged by inverted pendulum loading.

The stiffness of activated muscles may stabilize a loaded joint by preventing perturbations from causing large displacements and injuring the joint. Here the elbow muscle recruitment patterns were compared with the forearm loaded vertically (a potentially unstable inverted pendulum configuration) and with horizontal loading. Eighteen healthy subjects were studied with the forearm vertical and supinated and the elbow flexed approximately 90 degrees. In the first experiment EMG electrodes recorded activity of biceps, triceps, and brachioradialis muscles for joint torques produced (a) by voluntarily exerting a horizontal force isometrically (b) by voluntarily flexing and extending the elbow while the forearm was loaded vertically with 135N. The relationship between the EMG and the torque generated was quantified by the linear regression slope and zero-torque intercept. In a second experiment a vertical load increasing linearly with time up to 300N was applied. In experiment 1 the EMG-torque relationships for biceps and triceps had an intercept about 10% of maximum voluntary effort greater with the vertical compared to the horizontal force, the inverse was found for Brachioradialis, but the EMG-torque slopes for both agonist and antagonistic muscles were not different. In experiment 2 there were 29 trials with minimal elbow displacement and all the three muscles activated on the order of 11% of maximum activation to stabilize the elbow; 19 trials had small elbow extension and 14 trials small flexion requiring altered muscle forces for equilibrium; 7 trials ended in large unstable displacement or early termination of the test. An analysis indicate that the observed levels of muscle activation would only provide stability if the muscles' short-range stiffness was at the high end of the published range, hence the elbow was marginally stable. The stability analysis also indicated that the small elbow extension increased stability and flexion decreased stability.

Algorithms↗
PubMed1994

Influence of stabilization occlusal splint on craniocervical relationships. Part II: Electromyographic analysis.

The aim of this study was to determine the effect of stabilization occlusal splints on electromyographic (EMG) activity of sternocleidomastoid and trapezius muscles in subjects with spasm in the mentioned muscles. A full-arch maxillary stabilization occlusal splint was made for each of the 15 subjects. In the sternocleidomastoid muscle, tonic and saliva swallowing EMG activity decreased significantly with the splint, whereas maximal clenching activity did not change. In the trapezius muscle, no significant changes were observed with the occlusal splint. The different pattern in both muscles during tonic and swallowing EMG activity with the splint is attributed to differences in the synaptic inputs to the respective motoneuron pools, suggesting that a differential modulation of the motor neuron pools may exist of both muscles, of peripheral and/or central origin.

Adult↗
PubMed2006

Assessment of genetic stability of Brucella melitensis Rev 1 vaccine strain by multiple-locus variable-number tandem repeat analysis.

The assessment of the genetic stability is one of the essential elements to guarantee the biological quality of live anti-bacteria vaccines. Live attenuated Brucella melitensis Rev 1 is the most effective vaccine against brucellosis in small ruminants. Thirty-six B. melitensis Rev 1 vaccine strains isolated from human or animal sources from different geographic regions, from different commercial batches or laboratory collections were typed by the multiple-locus variable-number tandem repeat (VNTR) analysis (MLVA) recently described for Brucella spp. Our results demonstrated that B. melitensis Rev 1 group as assayed by MLVA is genetically very homogeneous. We believe that MLVA methodology could be an essential assay to guarantee the quality and stability of live anti-bacterial vaccines being produced worldwide and can be included as in vitro control.

Animals↗
PubMed1986

Failure of stabilization of the spine with methylmethacrylate. A retrospective analysis of twenty-four cases.

Twenty-four patients who had a major complication after attempted stabilization of the spine with methylmethacrylate were referred for treatment. The initial instability that necessitated stabilization was caused by a traumatic condition in fifteen of these patients and by a metastatic tumor in nine. The average length of time before failure of fixation was 208.3 days for the patients who had a traumatic condition and 193.7 days for those who had a neoplasm. In eleven patients a progressive neural deficit developed postoperatively, and in six others the recovery of neural function was possibly hindered by the cement. A deep wound infection developed in six patients, and in five of them treatment by removal of the methylmethacrylate and metal, followed by a prolonged period of cervical traction, was required. Loosening and failure of fixation was the most common complication--it occurred in twelve of the fifteen patients who had a traumatic lesion and in eight of the nine who had a neoplasm. Salvage operations that included removal of the cement and conventional bone-grafting procedures were performed in eleven of the twelve patients who had loosening associated with a traumatic lesion and in six of the eight who had loosening and a tumor. Stability was restored in every patient. Improved long-term results can be achieved by using grafts of iliac bone and triple-wire stabilization methods (a midline wiring between the spinous processes and two iliac-crest grafts, one on each side, wired to the posterior elements) instead of methacrylate in the primary treatment of traumatic injuries. The treatment of choice for instability caused by neoplastic destruction of two or more vertebral bodies includes a construct of methylmethacrylate anteriorly. However, if cement is used, early augmentation with posterior fusion of the spine and stabilization should be considered. As a rule, combined anterior and posterior stabilization is recommended for the reconstruction of a spine that is unstable due to neoplastic destruction. In general, whenever methylmethacrylate is used for spinal stabilization, it should be augmented with grafts of iliac bone to provide long-term stability.

Adult↗
PubMed1991

Stability patterns and trophic structure in a Delaware Bay plankton community.

Using qualitative loop analysis we have extended our examination of a Delaware Bay plankton community to include an investigation of the roles played by the various entities (population, guild or nutrient) in the community. In an entity removal exercise, we used stability relationships as a probe into community structure. Six types of stability change are possible as a result of entity removal from the system: stable to stable (s-->s); stable to unstable (s-->u); stable to disconnected (s-->d); unstable to stable (u-->s); unstable to unstable (u-->u); unstable to disconnected (u-->d). Using these changes as an investigative tool, we found that in order to account for the stability-instability patterns, it was necessary to construct a refined trophic structure model. The observed connections between the entities in the larger model could be grouped into two different types of stability substructures: a simple pattern and a more complex branching pattern. These patterns map easily onto the refined trophic structure model. Using stability analysis it is also possible to model community structure in ways other than the traditional trophic approach. Patterns of system necessity and relative contribution to stability are observed. These patterns match the refined trophic structure model derived previously. The roles that the various entities play in the overall community were followed over an annual cycle. Entities were seen to change their roles as a function of time and status within a subgroup. These results show that stability determinations have the potential to be used as a valuable tool in community analysis.

Animals↗
PubMed2005

Resonance frequency analysis of one-stage dental implant stability during the osseointegration period.

BACKGROUND: Currently, there is no available clinical tool to evaluate the amount of osseointegration and stability around dental implants. It has been recently suggested that changes in the stiffness of an implant in bone during healing may be monitored by using resonance frequency analysis (RFA). The aim of this study was to determine whether RFA can be integrated into the routine clinical evaluation of initial healing of dental implants. METHODS: Thirty-one patients (18 female and 13 male; mean age of 51.7 years) were included into this study. A total of 122 implants and three different, but comparable, implant designs were evaluated by using RFA. The specific transducer for each implant system was used. ISQ (implant stability quotient) readings were obtained for each implant at the time of surgery, 3 and 6 weeks postoperatively, and at the time of loading (3 or 6 months following surgery). Data were analyzed for different healing times, various anatomical locations, implant length, and type. Average time in function was 12 months. RESULTS: Two implants failed during healing. Implant stability was higher on the mandible compared to the maxilla for each implant system studied (Mann-Whitney test, P <0.01). ISQ readings decreased significantly at 3 and 6 weeks post-surgery compared to readings obtained at surgery (Wilcoxon matched pairs sign-rank tests, P <0.01). A recovery to the initial ISQ levels was noted at the time of implant loading. The possible effects of different types and lengths of implants to ISQ readings were examined. CONCLUSIONS: Results of this study support the need for a clinical tool to evaluate dental implant stability prior to loading, especially for implants placed in the maxilla. It appears that implant stability is weakest at 3 to 6 weeks in one-stage non-loaded dental implants. ISQ readings can be used to determine different healing phases and the stability of dental implants. However, it is difficult to define a general standardized range of ISQ readings for successful implant integration for various implant systems. Thus, RFA values/ISQ levels should be calibrated for each implant system separately. Further studies are needed to compare the early changes seen in immediately loaded dental implants and to determine whether there is any time in which the total recovery in ISQ levels may occur.

Dental Implantation, Endosseous↗
PubMed1999

Analysis of negatively 'charge tagged' DNA by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

An improvement in detectability and stability of DNA analysis by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) using oligonucleotides modified with a neutralized backbone and a fixed single, positive charge was recently reported. The attachment of the positive charge requires a primary amino group, limiting this approach to accordingly functionalized DNA. The method described here uses backbone neutralized DNA for the same purpose, with a single unmodified phosphate in the DNA backbone carrying the negative charge. Thus, no chemical modification other than neutralizing the remaining charges on the phosphorothioates is required. This is performed in a single methylation step. The enhancement in sensitivity is comparable to that for DNA carrying a single positive charge, interestingly even when using the same non-protonating matrix. The mechanistic implications of these findings regarding the MALDI process are discussed. The DNA derivatization methods presented help to make MALDI-MS of DNA applicable and competitive for genome analysis and medical diagnostics.

DNA↗
PubMed1992

Transnational stability of gender differences in schizophrenia? An analysis based on the WHO study on determinants of outcome of severe mental disorders.

Gender-specific analyses of the multinational WHO-Determinants of Outcome-Study (including 1,292 cases from 10 countries) demonstrate the transnational stability of major findings on gender differences in schizophrenia: Male patients have an earlier mean age at onset in all countries. In female patients, the distribution of the age at onset shows a second peak after age 40 years. No gender differences on nuclear symptoms of schizophrenia can be detected, but on uncharacteristic symptoms, particularly some aspects of the illness behaviour, differences appear. This investigation supports the transcultural validity of gender differences found in the German ABC-Schizophrenia-Study and in the Danish-German Psychiatric Case Register studies.

Adult↗
PubMed2004

High-performance liquid chromatographic analysis of dextromethorphan, guaifenesin and benzoate in a cough syrup for stability testing.

A method has been developed for the analysis of a cough syrup containing dextromethorphan, guaifenesin, benzoic acid, saccharin and other components. Forced degradation was also studied to demonstrate that the method could be employed during a stability study of the syrup. Final conditions were phosphate buffer (25 mM, pH 2.8) with triethylamine (TEA)-acetonitrile (75:25, v/v). In such conditions, all the actives, excipients and degradation products were baseline resolved in less than 14 min, and different wavelengths were used for the different analytes and related compounds.

Acetonitriles↗
PubMedDate not supplied

Three-dimensional computerized stress analysis of commercially pure titanium and yttrium-partially stabilized zirconia implants.

PURPOSE: The purpose of this study was to use three-dimensional finite element analysis to analyze stress distribution patterns in Re-Implant implants made of commercially pure titanium (cpTi) and yttrium-partially stabilized zirconia (YPSZ). MATERIALS AND METHODS: Two three-dimensional finite element analysis models of a maxillary incisor with Re-Implant implants were made, surrounded by cortical and cancellous bone. A porcelain-fused-to-metal crown for the cpTi implant and a ceramic crown for the YPSZ implant were modeled. Stress levels were calculated according to the von Mises criteria. RESULTS: Higher stresses were observed at the area where the implant entered the bone. Stresses were higher at the facial and lingual surfaces than the proximal ones. In cortical bone and at the junction of cortical and cancellous bone, stress distribution presented a pattern of alternating higher (4.0 to 5.0 MPa) and lower (1.3 to 2.0 MPa) stress areas. Higher stresses were found at the apical third of the implant-to-bone junction as well. CONCLUSION: Re-Implant implants presented a pattern of low, well-distributed stresses along the entire implant-to-bone interface. YPSZ implants had very similar stress distribution to cpTi implants and may be viable esthetic alternatives, especially in maxillary anterior regions.

Ceramics↗
PubMed2003

Early-age-at-onset colorectal cancer and microsatellite instability as markers of hereditary nonpolyposis colorectal cancer.

PURPOSE: Early-age-at-onset colorectal cancer and microsatellite instability are characteristic features of hereditary nonpolyposis colorectal cancer. Our aim was therefore to investigate whether these features might be useful markers in screening for hereditary nonpolyposis colorectal cancer and mismatch repair gene mutations. METHODS: From 1,132 consecutive patients who underwent surgery for colorectal cancer at our department between 1980 and 1999, we selected all patients 40 years of age or younger (study group, n = 59) and a subset of patients 40 years of age or older (control group, n = 60) who were matched for gender and pathologic TNM stage. Patients for whom a complete family cancer history or microsatellite status was unavailable were excluded from the study. Family cancer histories, retrieved from archival charts, were reassessed. Microsatellite status was investigated with the five microsatellites from the Bethesda recommended panel (BAT-26, BAT-25, D2S123, D5S346, and D17S250). On the basis of the number of altered microsatellites (> or = 2, 1, or 0), tumors were considered as having high or low instability or microsatellite stability, respectively. Mutation analysis for MLH1 and MSH2 genes was performed only in cases of high instability. DNA was investigated for mutations by single-strand conformational polymorphism and sequencing analysis. RESULTS: Data from 95 patients (study group: n = 37, 18 males, mean age 35 years; control group: n = 58, 29 males, mean age 62 years) were available for analysis. Four patients (study group, n = 3; control group, n = 1) fulfilled the Amsterdam II criteria for hereditary nonpolyposis colorectal cancer. Of the 37 study group tumors, 12 (32.4 percent) showed high-frequency microsatellite instability, and 25 had microsatellite stability, whereas among the 58 control group tumors, 4 (7 percent) showed high-frequency microsatellite instability, and 54 had microsatellite stability (P < 0.002). Mismatch repair gene mutation analysis was performed in 12 cases (study group, n = 7; control group, n = 5). We found four mutations (MSH2 119delG, MLH1 ex9 684insT, MSH2 Gln239Stop, and MLH1 del0.8 Kb) in the study group patients and none in the control group. Of four hereditary nonpolyposis colorectal cancer patients who underwent mismatch repair gene mutation analysis, one had a mutation. CONCLUSIONS: Early-age-at-onset colorectal cancer is significantly correlated with high-frequency microsatellite instability tumor status and is a useful criterion to identify hereditary nonpolyposis colorectal cancer patients. Moreover, when used in association with high-frequency microsatellite instability status, it is effective in selecting patients for mismatch repair gene mutation analysis.

Adaptor Proteins, Signal Transducing↗
PubMed2002

Periodic deformations in nematic liquid crystals.

We reconsider the possibility of periodic deformations in nematic liquid crystal samples, and present a simple method to analyze their stability near the threshold. Our method consists in finding the matrix characterizing the total energy in terms of the integration constants of the linearized solutions of the variational problem. In the undeformed state all the integration constants are identically zero. Hence the analysis of the stability of the undeformed state reduces to the analysis of the sign of the determinants of the principal minors of the matrix of the quadratic form representing the total energy of the nematic sample. We discuss the role of the saddle-splay elastic constant and of the anchoring energy strength in the stability of the modulated structure. The role of the thickness of the sample, as well as of the polar and azimuthal anchoring energies, in the phenomenon is also considered.

Journal Article↗
PubMed1998

Contribution of hydrogen bonds to the conformational stability of human lysozyme: calorimetry and X-ray analysis of six tyrosine --> phenylalanine mutants.

The contribution of hydrogen bonds to the conformational stability of human lysozyme was investigated by the combination of calorimetric and X-ray analyses of six Tyr --> Phe mutants. Unfolding Delta G and unfolding Delta H values of the Tyr --> Phe mutant proteins were changed by from +0.3 to -4.0 kJ/mol and from 0 to -16 kJ/mol, respectively, compared to those of the wild-type protein. The net contribution of a hydrogen bond at a specific site to stability (Delta Gwild/HB), considering factors affected by substitutions, was evaluated on the basis of X-ray structures of the mutant proteins. In the present study, one of six mutant proteins was suitable for evaluating the strength of the hydrogen bond. Delta Gwild/HB for the intramolecular hydrogen bond at Tyr124 was evaluated to be 7.5 kJ/mol. Results of the analysis of other mutants also suggest that hydrogen bonds of the hydroxyl group of Tyr, including the hydrogen bond with a water molecule, contribute to the stabilization of the human lysozyme.

Calorimetry, Differential Scanning↗
PubMed1993

Breakdown in the relationship between thermal and thermodynamic stability in an interleukin-1 beta point mutant modified in a surface loop.

Sequence variants of the beta-barrel protein interleukin-1 beta have been analyzed for their stabilities toward irreversible thermal inactivation by monitoring the generation of light scattering aggregates on heating. The derived temperatures for the onset of aggregation (T(agg) values) correlate well with the free energies of unfolding of these proteins with the exception of one variant, Lys97-->Val (K97V), which undergoes aggregation at a temperature 7 degrees C lower than expected based on its thermodynamic stability. This lower than expected thermal stability may be due to generation of an aggregation-prone unfolding intermediate at a temperature lower than the Tm of the global transition. This hypothesis is supported by the location of residue 97 in the long 86-99 loop which has structural features suggesting it may comprise a small, independent folding unit or microdomain. The excellent correlation of thermal and thermodynamic stabilities of seven of the eight variants tested is consistent with accepted models for thermal inactivation of proteins. At the same time the poor fit of the K97V variant underscores the risk in using thermal stability data in quantitative analysis of mutational studies of the folding stability of proteins.

Crystallography, X-Ray↗
PubMed2002

Stability of a recombinant adenoviral vector: optimization of conditions for storage, transport and delivery.

Recombinant viral vectors have been developed for use as therapeutic agents and for the introduction of exogenous genes into living cells. However, little is known about the viability and stability of such recombinant viruses during storage, transport and delivery under various conditions. We describe here an analysis of the stability of an adenoviral vector in crude solutions of cell lysates during freezing and thawing and during storage at various temperatures in the presence and in the absence of glycerol. For example, the titer of adenoviruses in crude lysates of infected cells was reduced only ten-fold or three-fold after two hundred rounds of freezing and thawing or after incubation at 28 degrees C for 14 days, respectively. Our observations indicate that recombinant adenoviral vector was more stable than expected both during freezing and thawing and during storage at low temperatures. Our results confirm the importance of appropriate conditions for the delivery and transport of recombinant adenoviral vectors.

Adenoviridae↗